Dietary Cardamom Inhibits the Formation of Azoxymethaneinduced Aberrant Crypt Foci in Mice and Reduces COX-2 and iNOS Expression in the Colon

Recently, considerable attention has been focused on identifying naturally occurring chemopreventive compounds ‍capable of inhibiting, retarding, or reversing the multi-step carcinogenesis. The primary aim of the present study ‍was to identify the effects of a commonly consumed spice, viz., cardamom against azoxymethane (AOM) induced ‍colonic aberrant crypt foci (ACF) in Swiss Albino mice. The secondary aim, was to explore the ability of cardamom ‍to modulate the status of proliferation and apoptosis, and to understand its role in altering cyclooxygenase-2 (COX- ‍2) and inducible nitric oxide synthase (iNOS) expression. Male Swiss albino mice were injected with AOM (dose: ‍5mg/Kg body weight) or saline (Group 1) weekly once for two weeks. The AOM-injected mice were randomly assigned ‍to two groups (Groups 2 and 3). While all the groups were on standard lab chow, Group 3 received oral doses of ‍0.5% cardamom, in aqueous suspension, daily for 8 weeks. Following treatment, significant reduction in the incidences ‍of aberrant crypt foci (p<0.05) was observed. This reduction in ACF was accompanied by suppression of cell ‍proliferation (mean Brdu LI in carcinogen control=13.91+3.31, and 0.5%cardamom=2.723+0.830) and induction of ‍apoptosis (mean AI in carcinogen control=1.547+0.42 and 0.5% cardamom= 6.61+0.55). Moreover, reduction of ‍both COX-2 and iNOS expression was also observed. These results suggest that aqueous suspensions of cardamom ‍have protective effects on experimentally induced colon carcinogenesis. Cardamom as a whole and its active ‍components require further attention if the use of this spice is to be recommended for cancer prevention.     

Suppression of Azoxymethane-induced Colonic Premalignant Lesion Formation by Coenzyme Q10 in Rats

Reactive oxygen species cause damage to proteins, lipids and DNA. Coenzyme Q10 (CoQ10) is a compound withmitochondrial bioenergetic functions. The reduced form of CoQ10 shows antioxidant activity. In the present study,effects of CoQ10 on development of azoxymethane (AOM)-induced aberrant crypt foci (ACF) and mucin-depletedfoci (MDF) in F344 male rats were investigated. To induce ACF and MDF, 6-week old rats were given two weeklysubcutaneous injections of AOM (15 mg/kg body weight) and also received a control diet or experimental dietscontaining CoQ10 (200 or 500 ppm) for 4 weeks, starting one day before the first dose of AOM. At 10 weeks of age,all animals were sacrificed and their colons were evaluated for numbers and sizes of ACF and MDF. Administrationof 200 and 500 ppm CoQ10 resulted in reduction of ACF numbers, to 77% and 68% of the carcinogen control value,respectively. The percentages of ACF consisting of more than 4 crypts in these groups were also significantly lowerthan in the controls. Treatment with 500 ppm CoQ10 furthermore decreased the number of sialomucin-producingACF and MDF per colon to 42% and 38% of the carcinogen control value without CoQ10, respectively. Theseresults suggest that CoQ10 may be an effective chemopreventive agent against colon carcinogenesis.     

Suppressive Effect of Pioglitazone,a PPAR Gamma Ligand,on Azoxymethane-induced Colon Aberrant Crypt Foci in KK-Ay Mice

Obesity is an established risk factor for colorectal cancer. Pioglitazone is a peroxisome proliferatoractivatedreceptorγ (PPARγ) agonist that induces differentiation in adipocytes and induces growth arrestand/or apoptosis in vitro in several cancer cell lines. In the present study, we investigated the effect ofpioglitazone on the development of azoxymethane-induced colon aberrant crypt foci (ACF) in KK-Ayobesity and diabetes model mice, and tried to clarify mechanisms by which the PPARγ ligand inhibitsACF development. Administration of 800 ppm pioglitazone reduced the number of colon ACF / mouseto 30% of those in untreated mice and improved hypertrophic changes of adipocytes in KK-Ay mice withsignificant reduction of serum triglyceride and insulin levels. Moreover, mRNA levels of adipocytokines,such as leptin, monocyte chemoattractant protein-1 and plasminogen activator inhibitor-1, in the visceralfat were decreased. PCNA immunohistochemistry revealed that pioglitazone treatment suppressed cellproliferation in the colorectal epithelium with elevation of p27 and p53 gene expression. These results suggestthat pioglitazone prevented obesity-associated colon carcinogenesis through improvement of dysregulatedadipocytokine levels and high serum levels of triglyceride and insulin, and increase of p27 and p53 mRNAlevels in the colorectal mucosa. These data indicate that pioglitazone warrants attention as a potentialchemopreventive agent against obesity-associated colorectal cancer.     

Dietary Aloe Vera Gel Powder and Extract Inhibit AzoxymethaneinducedColorectal Aberrant Crypt Foci in Mice Fed a Highfat Diet

Aloe vera gel exhibits protective effects against insulin resistance as well as lipid-lowering and anti-diabeticeffects. The anti-diabetic compounds in this gel were identified as Aloe-sterols. Aloe vera gel extract (AVGE)containing Aloe-sterols has recently been produced using a new procedure. We previously reported that AVGEreduced large-sized intestinal polyps in Apc-deficient Min mice fed a high fat diet (HFD), suggesting that Aloevera gel may protect against colorectal cancer. In the present study, we examined the effects of Aloe vera gelpowder (AVGP) and AVGE on azoxymethane-induced colorectal preneoplastic aberrant crypt foci (ACF) in micefed a HFD. Male C57BL/6J mice were given a normal diet (ND), HFD, HFD containing 0.5% carboxymethylcellulose solution, which was used as a solvent for AVGE (HFDC), HFD containing 3% or 1% AVGP, and HFDCcontaining 0.0125% (H-) or 0.00375% (L-) AVGE. The number of ACF was significantly lower in mice given3% AVGP and H-AVGE than in those given HFD or HFDC alone. Moreover, 3% AVGP, H-AVGE and L-AVGEsignificantly decreased the mean Ki-67 labeling index, assessed as a measure of cell proliferation in the colonicmucosa. In addition, hepatic phase II enzyme glutathione S-transferase mRNA levels were higher in the H-AVGEgroup than in the HFDC group. These results suggest that both AVGP and AVGE may have chemopreventiveeffects on colorectal carcinogenesis under the HFD condition. Furthermore, the concentration of Aloe-sterolswas similar between 3% AVGP and H-AVGE, suggesting that Aloe-sterols were the main active ingredients inthis experiment.     

Inhibition of Azoxymethane-induced Colorectal Aberrant Crypt Foci in Mice Fed a High-fat Diet by Pleurotus eryngii (Eringi) and Hypsizygus marmoreus (Bunashimeji)

Obesity markedly increases the risk of colorectal cancer. Recently, the preventive effects of edible mushroomson triglyceride elevation and visceral fat accumulation have been reported. Here, the effects of Pleurotus eryngii(Eringi) and Hypsizygus marmoreus (Bunashimeji) on azoxymethane (AOM)-induced aberrant crypt foci (ACF;precancerous lesions) in the colorectums of mice fed a high-fat diet were examined. Eringi (ER) and Bunashimeji(BU) mushroom powder samples were used. Six-week-old male C57BL/6J mice received an intraperitonealinjection of AOM (10 mg/kg) once a week for two weeks, and were sacrificed and dissected at 6 weeks after thestart of the experiment. After the initiation of the experiment, they received a normal diet (ND), high-fat diet(HFD), HFD + ER (1 or 5% of diet), or HFD + BU (1 or 5% of diet). As a result, body and fat weights weresignificantly lower in the 5% ER and BU groups than in the HFD group. Liver triglyceride levels were alsosignificantly lower in the 5% ER and BU groups. Total liver cholesterol levels were significantly lower in the5% ER group. The numbers of ACF (especially large ACF) showed strong inhibitory effects in both ER and BUgroups. Measurement of the cell proliferation marker Ki-67 labeling index in the colonic mucosa demonstratedmore significant suppression in both ER and BU groups than in the HFD group. These results suggest that thesimultaneous intake of ER and BU may inhibit colorectal tumorigenesis in HFD-fed mice.     

Regressive Effects of Various Chemopreventive Agents on Azoxymethane-induced Aberrant Crypt Foci in the Rat Colon

Regressive effects of four chemopreventive agents [5-hydroxy-4-(2-phenyl-( E )-ethenyl)-2(5 H fura-none (KYN-54), S-methyl metbanethiosulfonate (MMTS), chlorogenic acid (CA), and piroxicam] on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in the colon of male F344 rats were examined by dietary exposure. At six weeks of age, 60 rats of groups 1 through 5 received subcutaneous injections of AOM (15 mg/kg body weight) once a week for three weeks. Twelve weeks after the first carcinogen injection, wben the occurrence of ACF was maximal, the rats in groups 2 through 5 were started on diet containing the test chemicals as follows: group 2, KYN-54 (0.02%); group 3, MMTS (0.01%); group 4, CA (0.025%); and group 5, piroxicam (0.0125%). Group 1 (20 rats) was kept on the basal diet alone, and group 6 (12 rate) served as an untreated control. Rats in each group were killed at 6, 12, 18, or 24 weeks after the start of the experiment, and the yield of ACF in the colon of each group at 18 or 24 weeks was compared with that at 12 weeks. The number of ACF per rat colon of each group at 18 or 24 weeks was smaller than that at 12 weeks. The reduction rates at 18 weeks were 7% in group 1 (AOM alone), 11% in group 2 (AOM+KYN-54), 10% in group 3 (AOM+MMTS), 51% in group 4 (AOM + CA) ( P 0.01), and 33% in group 5 (AOM+piroxicam) ( P <0.02), while at 24 weeks they were 12%, 26%, 51% ( P <0.002), 43% ( P <0.05), and 70% ( P <0.001), respectively. These results indicate that chemopreventive agents for large bowel carcinogenesis, i.e., KYN-54, MMTS, CA, and piroxicam, are not only able to prevent the development of ACF, but also can regress ACF, which are regarded as precursor lesions of colorectal cancer.     

Effects of Grape Juice in Superoxide Dismutase and Catalase in Colorectal Cancer Carcinogenesis Induced by Azoxymethane

Background: The intestinal mucosa is commonly exposed to oxidant nutrients and carcinogens, which can lead tothe generation of free radicals. The antioxidants present in the diet assume great importance as possible protectiveagents, reducing the oxidative damage. In this way, we evaluated the antioxidant action of grape juice on preneoplasticlesions induced by azoxymethane (AOM) in Wistar rats. Methods: The colorectal carcinogenesis was induced by twointraperitoneal injections of 15mg/kg of AOM in Wistar rats. The animals were divided in 7 groups and treated with1 and 2% concentrations of grape juice before and after carcinogen administration. After euthanasia, the expression ofantioxidant enzymes catalase (CAT), copper-zinc superoxide dismutase (Cu/Zn-SOD) and manganese superoxidedismutase (Mn-SOD) CAT, SOD1 and SOD2 were evaluated by immunohistochemistry. Results: AOM decreased theexpression of CAT and Mn-SOD enzymes, but not for Cu/Zn-SOD. We observed an increase expression of CAT andMn-SOD after grape juice administration in some concentrations according to the time of administration of the grapejuice before the carcinogen or just after the carcinogen. Conclusion: Our results suggest an independent action of eachenzyme and a possible antioxidant action of the grape juice components in the diet being able to balance the body toneutralize the superoxide radicals and not leave them in the cell-damaging form.     

Induction of Aberrant Crypt Foci and Flat-type Adenocarcinoma in the Colons of Dogs by N-Ethyl-N'-nitro-N-nitrosoguanidine and Their Sequential Changes

Sequential endoscopic observation of dog colons was performed during colon carcinogenesis. Two beagle dogs were given suppositories containing N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) every day for five months. In month 3, aberrant crypt foci (ACF), a putative preneoplastic lesion, were found in the colons of both dogs, but not in an untreated dog. The frequency of ACF increased until month 10, and then decreased. In month 9, very small lesions, less than 1 mm in diameter, which were similar to human early flat tumors, were first noticed. One of these lesions grew to about 7 mm in size without a change in its shape for 10 months. There were more than ten flat-type tumors in the two dogs, but such lesions were not found in the untreated dog. By biopsy, two of the lesions were proved to be well-differentiated adenocarcinomas histologically. Four polypoid lesions were found in one of the carcinogen-treated dogs. Thus, flat-type adenocarcinomas were induced in the dog colon by ENNG, and their development was followed by magnifying endoscopy.     

Nabag (Zizyphus spina-christi) Extract Prevents Aberrant Crypt Foci Development in Colons of Azoxymethane-Treated Rats by Abrogating Oxidative Stress and inducing Apoptosis

Zizyphus spina-christi (ZSC) fruit is a rich source of bioactive compounds but any medicinal properties inchemoprevention of colon cancer have hitherto not been studied. The aim of the present study was to examinein vivo protective effects of ZSC water extract on colon carcinogenesis in azoxymethane (AOM)–treated rats.Our results showed that ZSC significantly reduced AOM-induced colonic aberrant crypt foci development andAOM-induced oxidative stress as indicated by restoration of endogenous glutathione depletion and abrogating theimpairment of total antioxidant capacity. Caspase-3 cleavage, which has been considered as an apoptotic index,was almost undetectable in AOM-treated rats and ZSC exhibited pro-apoptotic effects evidenced by increasedlevels of cleaved caspase-3. In the studied model, our findings provide the first in vivo evidence that ZSC extractcould inhibit the early stage of colon carcinogenesis by preventing oxidative stress and inducing apoptosis.     

Effects of Two Traditional Chinese Cooking Oils,Canola and Pork,on pH and Cholic Acid Content of Faeces and Colon Tumorigenesis in Kunming Mice

Faecal pH and cholate are two important factors that can affect colon tumorigenesis, and can be modifiedby diet. In this study, the effects of two Chinese traditional cooking oils (pork oil and canola/rapeseed oil) on thepH and the cholic acid content in feces, in addition to colon tumorigenesis, were studied in mice. Kunming micewere randomized into various groups; negative control group (NCG), azoxymethane control group (ACG), porkoil group (POG), and canola oil Ggroup (COG) . Mice in the ACG were fed a basic rodent chow; mice in POGand COG were given 10% cooking oil rodent chow with the respective oil type. All mice were given four weeklyAOM (azoxymethane) i.p. injections (10mg/kg). The pH and cholic acid of the feces were examined every twoweeks. Colon tumors, aberrant crypt foci and organ weights were examined 32 weeks following the final AOMinjection. The results showed that canola oil significantly decreased faecal pH in female mice (P<0.05), but hadno influence on feces pH in male mice (P>0.05). Pork oil significantly increased the feces pH in both male andfemale mice (P<0.05). No significant change was found in feces cholic acid content when mice were fed 10%pork oil or canola oil compared with the ACG. Although Kunming mice were not susceptible to AOM-inducedtumorigenesis in terms of colon tumor incidence, pork oil significantly increased the ACF number in male mice.Canola oil showed no influence on ACF in either male or female mice. Our results indicate that cooking oil effectsfaecal pH, but does not affect the faecal cholic acid content and thus AOM-induced colon neoplastic ACF ismodified by dietary fat.     

Grapefruit Juice Suppresses Azoxymethane-induced Colon Aberrant Crypt Formation and Induces Antioxidant Capacity in Mice

In the present report we determined the protective capacity of grapefruit juice (GJ) against molecular andcellular damage in azoxymethane (AOM) treated mice. Animals were daily administered GJ orally (0.8, 4.1, and8.2 μl/g) for seven weeks, as well as intraperitoneally (ip) injected with AOM twice (weeks 2 and 3 of the assay).Control groups administered with water, with the high dose of GJ, and with AOM injected in weeks 2 and 3were also included. The results showed a significant, dose-dependent protection of GJ on the number of colonaberrant crypts (AC) induced by AOM. The highest inhibitory effect was reached with the highest tested doseof GJ, decreasing ACF by 51% and 43% at weeks 4 and 7 of the assay. Regarding protein and lipid oxidationwe also found a dose-dependent decrease caused with GJ in comparison with the increased levels produced byAOM. Therefore, our results established chemopreventive potential for GJ, and suggested effects related to itsantioxidant capacity. Finally, we found that the tested agents induced neither micronuclei increase nor alterationin bone marrow cytotoxicity.     

Unpolished Thai Rice Prevents ACF Formation and Dysplastic Progression in AOM-Induced Rats and Induces Apoptosis Through Redox Alteration in CaCo-2 Cells

Oxidative stress is associated with colon carcinogenesis including aberrant crypt foci (ACF) formationand it plays an important role in pathophysiological changes in cancer cells. The aims of this study were toinvestigate the effects of dietary unpolished Thai rice (UTR) on ACF formation and dysplastic progression inazoxymethane (AOM)-treated rats. Anti-cancer efficacy of UTR regarding apoptotic induction and oxidativeredox status in human colon cancer (CaCo-2) cells was also investigated. Rats given 20% and 70% of UTR inthe diet showed significantly and dose-dependently decreased total number of ACF. UTR treatment also wasstrongly associated with the low percentage of dysplastic progression and mucin depletion. In addition, wefound that UTR significantly induced cancer cell apoptosis, increased cellular oxidants, and decreased the levelof GSH/GSSG ratio in CaCo-2 cells. Our study suggests that UTR supplementation may be a useful strategyfor CRC prevention with the inhibition of precancerous progression, with induction of cancer cell apoptosisthrough redox alteration.     

Canola Oil Influence on Azoxymethane-induced Colon Carcinogenesis,Hypertriglyceridemia and Hyperglycemia in Kunming Mice

Azoxymethane (AOM) is a potent genotoxic carcinogen which specifically induces colon cancer. Hyperlipidemiaand diabetes have several influences on colon cancer development, with genetic and environmental exposureaspects. Here, we investigated plasma lipid and glucose concentrations in Kunming mice randomized into fourgroups; control (no AOM or oil exposure), AOM control, AOM + pork oil, and AOM + canola oil. Aberrantcrypt foci (ACF), plasma cholesterol, plasma triglyceride, plasma glucose and organ weight were examined 32weeks after AOM injection. Results revealed that AOM exposure significantly increased ACF number, plasmatriglyceride and glucose level. Further, male mice displayed a much higher plasma triglyceride level than femalemice in the AOM control group. Dietary fat significantly inhibited AOM-induced hypertriglyceridemia, andcanola oil had stronger inhibitory effect than pork oil. AOM-induced hyperglycemia had no sex-difference andwas not significantly modified by dietary fat. However, AOM itself not change plasma cholesterol level. AOMsignificantly increased liver and spleen weight in male mice, but decreased kidney weight in female mice. Onthe other hand, mice testis weight decreased when fed canola oil. AOM could induce colorectal carcinogenesis,hypertriglyceridemia and hyperglycemia in Kunming mice at the same time, with subsequent studies requiredto investigate their genome association.     

Preventive Effects of a Flavonoid Myricitrin on the Formation of Azoxymethane-induced Premalignant Lesions in Colons of Rats

The preventive effect of dietary exposure to a flavonoid myricitrin of azoxymethane (AOM)-induced aberrantcrypt foci (ACF) and beta-catenin-accumulated crypts (BCAC) formation was investigated in male F344 rats.Thirty-four rats were divided randomly into five experimental groups. Rats in groups 1-3 were given subcutaneousinjections of AOM (15 mg/kg body weight) once a week for 3 weeks. Starting 1 week before the first injection ofAOM, rats in groups 2 and 3 were fed a diet containing 500 or 1000 ppm myricitrin, respectively, for 11 weeks.Rats in group 4 were fed a diet containing 1000 ppm myricitrin. Rats in groups 1 and 5 were given the basal dietalone during the study. The experiment was terminated 11 weeks after the start. The frequency of ACF per colonin group 3 treated with AOM and 1000 ppm myricitrin was significantly lower than that in group 1 treated withAOM alone (p<0.01). Furthermore, dietary myricitrin at both doses (groups 2 and 3) significantly inhibited theformation of BCAC when compared to group 1 (p<0.05). These results indicate that myricitrin had possiblechemopreventive effects in the present short-term colon carcinogenesis bioassays and suggest that longer exposuremay cause suppression of tumor development.     

Gelam Honey and Ginger Potentiate the Anti Cancer Effect of 5-FU against HCT 116 Colorectal Cancer Cells

The development of chemopreventive approaches using a concoction of phytochemicals is potentially viablefor combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferativeeffects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil)against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growthof HCT 116 cells more potently (IC50 of 3mg/mL) in comparison to Gelam honey (IC50 of 75mg/mL). Combinedtreatment of the two compounds (3mg/mL ginger+75mg/mL Gelam honey) synergistically lowered the IC50 ofGelam honey to 22mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibitingeffects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggestedthat individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition,treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dosedependentlywhile treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes.Combination index analysis showed the combination effect of both natural compounds to be synergistic in theirinhibitory action against HCT 116 colon cancer cells (CI 0.96 < 1). In conclusion, combined treatment of Gelamhoney and ginger extract could potentially enhance the chemotherapeutic effect of 5-FU against colorectal cancer.     

Suppressing Effects of 6-(2,5-Dichlorophenyl)-2,4-diamino-1,3,5-triazine and Related Synthetic Compounds on Azoxymethane-induced Aberrant Crypt Foci in Rat Colon

The modifying effects of dietary administration of 6-(2,5-dichlorophenyl)-2,4-diamino-1,3,5-triazine and 5 related compounds on the occurrence of azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) were investigated in rats. Male F344 rats were given s.c. injections of AOM (15 mg/kg body weight) once a week for 3 weeks to induce ACF. They also received the diet containing 200 ppm test compound for 5 weeks, starting one week before the first dosing of AOM. At the termination of experiment, all of the compounds had caused a significant reduction in ACF frequency, which might be associated with suppression of the expression of proliferation biomarkers. The apoptotic index in the colonic mucosal epithelium of rats killed at 6 h after the first AOM exposure revealed no blocking activity of the compounds.     

Activity and Toxicity of Eleutherine palmifolia (L.) Merr. Extract on BALB/c Mice Colitis-Associated Colon Cancer Model

Objective: Eleutherine palmifolia (L.) Merr. extract (EPE) containing isoliquiritigenin and oxyresveratrol is believed to be an anticancer agent. This study evaluates colon histopathology, TNF-α, TGF-β, and hepatotoxicity on BALB/c mice colitis-associated colon cancer (CAC) model treated with EPE. Methods: In vivo study was performed on BALB/c mice CAC model induced by 10 mg/kgBW AOM on the first day followed by administration that each cycle consisted of 5% DSS in water for seven days and regular water for seven days. The indicators of the formation of CAC were observed by a fecal occult blood test (FOBT) and serum amyloid α (SAA) test. The treatment was conducted once a week started from the seventh week up to the twentieth week with six treatment groups: I was administrated by regular water only (negative control), II was administrated by AOM and DSS only (positive control), III was administrated by doxorubicin,  IV-VI were treated by EPE (0.25 mg/kg BW, 0.50 mg/kg BW, and 1.00 mg/kg BW) respectively. The colon and liver’s histopathology was observed using hematoxylin-eosin (HE) staining, TNF-α with immunohistochemistry (IHC), and level measurement of TGF-β colon with ELISA reader. The data were used one-way ANOVA followed by post hoc as statistical analysis. Results: The administration of EPE increased the expression of TNF-α, the total of goblet cells of the colon, and decreased the level of TGF-β. Administration of EPE 0.50 mg/20g BW decreased a liver histopathological score but induced a histopathological alteration of the liver at a dose of 1.00 mg/20g BW. Conclusion: This study indicate that EPE could be recommended as a colon anticancer through increase the goblet cells, induce apoptosis through increase TNF-α, and decrease TGF-β.     

手术操作对大肠癌患者肿瘤细胞血行扩散的影响

目的　探讨手术对大肠癌血行扩散的影响。方法　对 2 3例行根治手术切除的大肠癌患者 ,分别于肿瘤切除前后采取外周静脉血 ,采用巢式RT PCR方法检测血中CEAmRNA表达情况。同时取该患者的肿瘤组织作阳性对照 ,以 2 0例正常人外周血作阴性对照。结果　手术前后外周血中CEAmRNA阳性表达率分别为 3 4.8%和 69.6% (P =0 .0 4)。 91.3 % ( 2 1/ 2 3 )的病例肿瘤组织CEAmRNA表达呈阳性。 2 0例正常人外周血中CEAmRNA均为阴性。结论　手术操作可促进大肠癌肿瘤细胞的血行扩散     

Effect of 5-Fluorouracil and UFT on Experimental Liver Metastasis Model of Colorectal Cancer Using Mouse Colon 26 Cells

Effects of 5-fluorouracil (5-FU) and UFT on an experimental liver metastasis model were compared at equi-effective dosage levels against subcutaneous tumor of mouse colon 26. 5-FU at the dosage level of 40 mg/kg suppressed the subcutaneous tumor growth by 70.0% and 45.0% on day 13 and day 18, respectively, and UFT at 20 mg/kg provided almost equal suppression (63.0% and 48.0%). In the liver metastasis model, 5-FU at 40 mg/kg showed more potent prevention of the formation of metastatic foci (94.9%) than did UFT (60.4%) at 20 mg/kg. 5-FU at 40 mg/kg produced a much higher peak serum level of 5-FU than did UFT at 20 mg/kg and also showed a much higher AUC (area under the curve) level in the portal blood. These results suggest that oral administration of 5-FU might be useful in prevention of liver metastasis of colorectal cancer.     

苦参碱对大肠癌细胞凋亡及Bax、Bcl-2表达的影响

[目的]探讨苦参碱对人大肠癌Lovo细胞增殖抑制和凋亡诱导作用及其对Bax、Bcl-2表达的影响。[方法]0.05~1.6mg/ml不同浓度苦参碱作用Lovo细胞,采用MTT法检测苦参碱对大肠癌Lovo细胞增殖抑制作用,DNAladder、AnnexinⅤ-PI法及TUNEL染色检测细胞凋亡,WesternBlot法检测凋亡相关蛋白Bax、Bcl-2表达的变化。[结果]0.05～1.6mg/ml苦参碱处理Lovo细胞24h或48h后,细胞增殖均明显受抑制;DNAladder、AnnexinⅤ-PI法及TUNEL染色检测结果显示苦参碱呈时间、剂量依赖性诱导细胞凋亡;促凋亡蛋白Bax随着苦参碱剂量增加表达增加,抗凋亡蛋白Bcl-2随着苦参碱剂量增加表达减少。[结论]苦参碱具有抑制大肠癌细胞增殖,诱导其凋亡的作用。苦参碱诱导大肠癌细胞凋亡的机制可能与促凋亡蛋白Bax表达增加、抗凋亡蛋白Bcl-2表达减少有关。