Evaluation of antitumor and toxic side effects of mitomycin C-estradiol conjugates

The antitumor and toxic side effects of mitomycin C-estradiol conjugates (EB-glu-MMC and E-glu-MMC) were evaluated in detail for solutions in propylene glycol and suspensions in 10% (v/v) propylene glycol. Tumor growth, body weight and number of leukocytes were examined after i.p. administration to sarcoma 180 solid tumor-bearing mice. Body weight and number of leukocytes were also examined in normal mice after i.p. administration of the solution. In solution dosage forms, the two conjugates had almost the same suppressive effect on tumor growth at 30 mg MMC eq./kg as MMC at 5 mg/kg, did not lower body weight significantly, but reduced the number of leukocytes at 30 mg MMC eq./kg. MMC, lethally toxic at 10 mg, significantly lowered the body weight and leukocyte number. In the suspension dosage forms, these conjugates had a greater suppressive effect on tumor growth at 50 mg MMC eq./kg than MMC at 5 mg/kg, and reduced the body weight and leukocyte number, with E-glu-MMC more toxic than EB-glu-MMC. The presence of the tumor itself influenced the body weight and leukocyte number. However, toxic side effects could be evaluated from the body weight and leukocyte number to almost the same extent between tumor-bearing and normal mice.     

螺旋藻多糖硫酸酯化修饰前后抗肿瘤及免疫活性的研究

比较螺旋藻多糖硫酸酯化修饰前后体内外抗肿瘤及免疫活性.采用MTT比色法研究药物在体外对人肿瘤细胞株的抑制作用,促进正常小鼠脾淋巴细胞的增殖活性以及对荷瘤小鼠NK和CTL细胞活性的影响.采用移植性肿瘤实验方法考察了药物对小鼠S180肉瘤的抑制作用.结果显示,螺旋藻多糖（NPSP）对肿瘤细胞株几乎无细胞毒作用,硫酸酯化螺旋藻多糖（SNPSP）对肿瘤细胞株具有显著的细胞毒作用,其中对SMMC-7721人肝癌细胞株抑制率最高达50%.NPSP50 mg/kg对小鼠S180肉瘤无抑制,相同剂量的SNPSP对小鼠S180肉瘤的抑制率达35.42%.NPSP具有促进脾淋巴细胞增殖作用,但对ConA和LPS诱导的脾淋巴细胞增殖反应无促进作用,SNPSP促进脾淋巴细胞增殖作用较NPSP增强,同时对ConA和LPS诱导的脾淋巴细胞增殖反应也具有明显的促进作用.NPSP和SNPSP均能促进荷瘤小鼠NK细胞和CTL细胞活性,其中SNPSP促进CTL细胞活性较NPSP增强.     

In vivo investigation of tolerance and antitumor activity of cisplatin-loaded PLGA-mPEG nanoparticles

The tolerance of BALB/c mice to different doses of blank and cisplatin-loaded PLGA-mPEG nanoparticles and the in vivo anticancer activity of these nanoparticles on SCID mice xenografted with colorectal adenocarcinoma HT 29 cells were investigated. Nanoparticles with an average size of 150-160 nm and approximately 2% w/w cisplatin content were prepared by a modified emulsification and solvent evaporation method. Normal BALB/c mice tolerated three weekly intravenous injections of a relatively high dose of blank PLGA-mPEG nanoparticles (500 mg/kg, equivalent to about 10 mg nanoparticles/mouse) and three weekly intravenous injections of a high dose of nanoparticle-entrapped cisplatin (10 mg/kg). Also, histopathology examination indicated that there were no differences in the kidneys or spleens from animals treated with cisplatin-loaded nanoparticles or blank nanoparticles compared to the untreated control group. A moderate granulation of protoplasm of hepatic cells was observed in the livers from mice treated with cisplatin-loaded nanoparticles and blank nanoparticles, however, both the hepatic lobe and the portal hepatis maintained their normal architecture. The cisplatin-loaded PLGA-mPEG nanoparticles appeared to be effective at delaying tumor growth in HT 29 tumor-bearing SCID mice. The group of mice treated with cisplatin-loaded nanoparticles exhibited higher survival rate compared to the free cisplatin group. The results justify further evaluation of the in vivo antitumor efficacy of the PLGA-mPEG/cisplatin nanoparticles.     

Potential bioreductive alkylating agents. 5. Antineoplastic activity of quinoline-5,8-diones, naphthazarins, and naphthoquinones.

A number of 2-chloromethyl and 2-bromomethyl derivatives of naphthoquinones, quinolinediones, and naphthazarins were designed and synthesized as potential bioreductive alkylating agents, and the antitumor activity of these compounds was assessed in mice bearing Sarcoma 180 ascites cells. The results indicated that, with the exception of 3-benzamido-2-chloromethyl-1,4-naphthoquinone, which was inactive, all newly synthesized naphthoquinones possessed strong antitumor activity against this neoplasm. 6,7-Bis(bromomethyl)quinoline-5,8-dione had moderate inhibitory activity against Sarcoma 180 at its optimal daily dosage level of 15 mg/kg. 3-Bromo-2-bromomethyl- and 3-bromo-2-chloromethylnaphthazarin produced a moderate extension of the life span of tumor-bearing mice; whereas, in contrast, 6,7-dimethyl analogs of these agents were inactive when employed in daily doses up to 40 mg/kg body weight.     

聚酯型儿茶素的抗肿瘤及免疫调节作用

目的：研究聚酯型儿茶素（ＴＳ）对小鼠移植瘤的抑制作用及对荷瘤小鼠免疫功能的影响。方法：应用小鼠艾氏腹水癌实体型、小鼠Ｓ１８０肉瘤和肝癌Ｈ２２３种模型进行了ＴＳ的抗肿瘤作用研究;应用小鼠迟发型超敏反应模型、小鼠碳粒廓清试验及脾淋巴细胞增殖试验研究了 ＴＳ对荷Ｓ１８０小鼠免疫功能的影响。结果：４００、２００、５０ｍｇ／ｋｇ ＴＳ对小鼠艾氏腹水癌实体型瘤生长有明显抑制作用;常规灌胃给药对小鼠Ｓ１８０和肝癌Ｈ２２的生长无明显抑制作用,但预防给药则对小鼠Ｓ１８０和肝癌Ｈ２２的生长有明显抑制作用,各组抑瘤率均大于 ３０％。５０、１００、２００ｍｇ／ｋｇ ＴＳ可使荷瘤小鼠降低的迟发性超敏反应恢复正常;亦可使荷瘤小鼠碳粒廓清指数 Ｋ和吞噬指数α值显著提高;还可明显增强荷瘤小鼠脾Ｔ淋巴细胞增殖反应。结论：ＴＳ对小鼠移植瘤有明显抑制作用,同时可增强荷瘤小鼠降低的免疫功能。     

Antitumor activity of 2-amino-4,4alpha-dihydro-4alpha, 7-dimethyl-3H-phenoxazine-3-one against Meth A tumor transplanted into BALB/c mice

We examined the in vivo effect of 2-amino-4,4alpha-dihydro-4alpha,7-dimethyl-3H-phenoxazine-3- one (Phx) on Meth A carcinoma cells transplanted into BALB/c mice, in terms of both antitumor activity and side effects. Phx, which was synthesized by the reaction of 2-amino-5-methylphenol with bovine hemolysates, was administered i.p. at doses of 1 and 5 mg/kg to BALB/c mice transplanted with Meth A tumor cells. Phx exerted a strong antitumor activity to Meth A tumor growing in the mice as 5-fluorouracil (5-FU) did. The antitumor activity of Phx at the dose of 5 mg/kg was comparable to that of 5-FU at the dose of 7.8 mg/kg. In contrast, unlike 5-FU, Phx did not cause leukopenia while showing a strong antitumor activity. The compound also produced little changes in body weight and no wasting of mice developed. These results show that Phx has strong anti-tumor activity, but exerts lower side effects and suggest that Phx is available for therapeutic purposes in the future.     

Pharmacological study on kefir--a fermented milk product in Caucasus. I. On antitumor activity (1)]

The antitumor activity of kefir (YK-1), a fermented milk product in Caucasus, was investigated. YK-1 at oral doses of 100 or 500 mg/kg inhibited the proliferation of solid tumor of Ehrlich ascites carcinoma transplanted subcutaneously in mice. YK-1 did not show an inhibitory effect on the ear swelling induced contact dermatitis caused by picryl chloride (PC-CD). However, YK-1 inhibited the immunosuppression in Ehrlich carcinoma-bearing mice and with the frozen and dried ascites of the tumor-bearing mice containing immunosuppressive substances (EC-sup) in PC-CD-induced mice. And also, YK-1 activated the immunosuppressive activity of spleen cells of mouse treated with EC-sup. These results suggest that YK-1 may have antitumor activity against Ehrlich carcinoma and activate the immunosuppression with it.     

Sex dimorphism in antitumor response of chemotherapeutic drug cisplatin in a murine host-bearing a T-cell lymphoma

Previously we have demonstrated that in-vivo growth of a murine T-cell lymphoma of spontaneous origin designated as Dalton's lymphoma (DL) shows sex dimorphism (J Rep Immunol 2005; 65:17-32). It remained unclear, however, if DL growth in female and male tumor-bearing hosts also shows a sex-dependent differential susceptibility to the antitumor action of cancer chemotherapeutic drugs. In this study we have demonstrated that in-vivo administration of anticancer drugs: cisplatin or doxorubicin to the DL-bearing host results in a sex-dependent different antitumor activity of the drugs, causing a sex dimorphism in the antitumor response of the drugs with respect to tumor growth inhibition. The antitumor effect of both drugs was found to be better in male tumor-bearing hosts compared with female tumor-bearing hosts. The study also shows that DL cells obtained from male and female tumor-bearing hosts display a differential growth response to following treatment with cisplatin in vitro. Cell growth regulatory proteins: interleukin-2, interferon-gamma, tumor growth factor-beta, p53, caspase-activated DNase, vascular endothelial growth factor, and interleukin-2 receptor were found to be involved in the observed sex-specific response of DL cells to the antitumor action of cisplatin. Moreover, gonadal hormones: androgen, estrogen, and their specific antagonists flutamide and tamoxifen were found to directly modulate the cytotoxicity of cisplatin against DL cells in vitro. This study, therefore, suggests for the first time that the efficacy of cancer chemotherapeutic may vary in a sex-specific manner in a host-bearing a T-cell lymphoma.     

Regression of Dalton’s lymphoma in vivo via decline in lactate dehydrogenase and induction of apoptosis by a ruthenium(II)-complex containing 4-carboxy <Emphasis Type="Italic">N</Emphasis>-ethylbenzamide as ligand

A novel ruthenium(II)-complex containing 4-carboxy N-ethylbenzamide (Ru(II)-CNEB) was found to interact with and inhibit M4-lactate dehydrogenase (M4-LDH), a tumor growth supportive enzyme, at the tissue level. The present article describes modulation of M4-LDH by this compound in a T-cell lymphoma (Dalton’s Lymphoma: DL) vis a vis regression of the tumor in vivo. The compound showed a dose dependent cytotoxicity to DL cells in vitro. When a non toxic dose (10 mg/kg bw i.p.) of Ru(II)-CNEB was administered to DL bearing mice, it also produced a significant decline in DL cell viability in vivo. The DL cells from Ru(II)-CNEB treated DL mice showed a significant decline in the level of M4-LDH with a concomitant release of this protein in the cell free ascitic fluid. A significant increase of nuclear DNA fragmentation in DL cells from Ru(II)-CNEB treated DL mice also coincided with the release of mitochondrial cytochrome c in those DL cells. Importantly, neither blood based biochemical markers of liver damage nor the normal patterns of LDH isozymes in other tissues were affected due to the treatment of DL mice with the compound. These results were also comparable with the effects of cisplatin (an anticancer drug) observed simultaneously on DL mice. The findings suggest that Ru(II)-CNEB is able to regress Dalton’s lymphoma in vivo via declining M4-LDH and inducing mitochondrial dysfunction–apoptosis pathway without producing any toxicity to the normal tissues.     

Anticancer effects of the Chinese medicine matrine on murine hepatocellular carcinoma cells

Matrine is a component of the traditional Chinese medical herb Sophora flavescens Ait, which is widely used to treat diseases such as viral hepatitis, cardiac arrhythmia and skin inflammations. As indicated by previous reports, the molecular mechanism of matrine's anti-cancer effect has been poorly clarified. In this study, we used both in vitro and in vivo models to investigate matrine's antitumor effect and its possible molecular mechanisms. Murine hepatocellular carcinoma H22 cells were cultured in the presence of matrine at various concentrations (0.2 - 2.0 mg/mL). A dose-dependent antiproliferation effect was observed. The 50 % inhibitory concentration (IC (50)) was 0.6 mg/mL. Antiproliferation effects of matrine were associated with an increase in cells arrested in the G (1) phase of the cell cycle. Morphological changes, flow cytometric analysis and expression of the proapoptotic protein Bax indicated that this anticancer effect was mediated via apoptosis. In vivo antitumor efficacy was evaluated following S. C. inoculation of H22 cells in BALB/c mice. Matrine administrated I. P. resulted in strong in vivo anticancer activity. Our results showed that seven doses of matrine at 50 mg/kg/dose inhibited 60.7 % of tumor growth. Transmission electron microscope (TEM) analysis and histoimmunochemical staining for Bcl-2 and Bax proteins also indicated induction of apoptosis in tumor tissues by matrine. Taken together, our results demonstrate that matrine possesses strong antitumor activities in vitro and in vivo. Inhibition of cell proliferation and induction of apoptosis are the likely mechanisms responsible for matrine's antitumor activities.     

Immunopotentiation and antitumor effects of a ginsenoside Rg₃-fortified red ginseng preparation in mice bearing H460 lung cancer cells

Antitumor effects of a ginsenoside Rg(3)-fortified red ginseng preparation (Rg(3)-RGP) were investigated in human non-small cell lung carcinoma (H460) cells using in vitro cytotoxicity assay and in vivo nude mouse xenograft model. Immunomodulatory effects of the preparation were also assessed by measuring the facilitating activities on the nitric oxide (NO) release from peritoneal macrophages, in vitro and in vivo lymphocyte proliferation, and the carbon clearance from circulating blood. In a cell level, Rg(3)-RGP exerted H460 cytotoxicity and facilitated splenocyte proliferation at very high concentrations, without affecting NO production. However, oral administration of Rg(3)-RGP (100-300 mg/kg) enhanced carbon particle-phagocytic index of blood macrophages up to 360-397% of control value. In addition, Rg(3)-RGP significantly increased the splenocyte proliferation (23% at 100mg/kg). In tumor-bearing mice, 28-day oral treatment with Rg(3)-RGP (100mg/kg) remarkably suppressed the tumor growth, leading to the decrease of the tumor volume and weight by 30-31%, which was comparable to the effect (27-29% reduction) of doxorubicin (2mg/kg at 3-day intervals). While Rg(3)-RGP did not cause adverse effects, intravenous injection of doxorubicin markedly decreased body and testes weights, and exhibited severe depletion of spermatogenic cells in the atrophic seminiferous tubules. These results indicate that Rg(3)-RGP exerts antitumor activities via indirect immunomodulatory actions, without causing adverse effects as seen in doxorubicin.     

Antitumor Activity of the Methanol Extract of Hypericum hookerianum Stem Against Ehrlich Ascites Carcinoma in Swiss Albino Mice

A large number of plants belonging to the Hypericum family are known to possess strong antitumor properties. The methanol extract of H. hookerianum Wight and Arnott stem (MEHH) exhibited potent in vitro cytotoxic activity against various cancerous cell lines. In the present study, the high performance liquid chromatography (HPLC) standardized MEHH was tested for in vivo antitumor properties against Ehrlich ascites carcinoma (EAC) tumor bearing mice at 100, 200, and 400 mg/kg body weight doses given orally once daily for 14 days. The results indicate that administration of the extract not only increased the survival of animals with ascites tumor, decreased the body weight induced by the tumor burden, and reduced packed cell volume and viable tissue cell count, but also altered many hematological parameters changed during tumor progression, indicating the potent antitumor nature of the extract. Among the three doses tested, the 200 mg/kg body weight dose was found to be the most potent.     

Betulinic acid exerts immunoregulation and anti-tumor effect on cervical carcinoma (U14) tumor-bearing mice

Phytochemicals used in cancer therapy and prevention are an important source. Betulinic acid (BetA), a lupine-type pentacyclic triterpenoid saponin from plants, has shown anti-tumor activity in some cell lines in previous studies. In this paper, its anti-tumor effect and the possible mechanisms were investigated in U14 tumor-bearing mice. The results showed that BetA (100 mg/kg and 200 mg/kg) effectively suppressed tumor growth in vivo. Compared with the control group, BetA significantly improved the levels of IL-2 and TNF-alpha in tumor-bearing mice and increased the number of CD4+ lymphocytes subsets, as well as the ratio of CD4+/CD8+ at a dose of 200 mg/kg. Furthermore, treatment with BetA induced cells apoptosis in dose-dependent manner in tumor bearing mice, and inhibited the expression of Bcl-2 and Ki-67 protein while upregulated the expression of caspase-8 protein. The mechanisms by which BetA exerted anti-tumor effects might involve the induction of tumor cell apoptosis. This process is also related to improvement of body's immune response.     

Aegle marmelos (L.) Correa inhibits the proliferation of transplanted Ehrlich ascites carcinoma in mice

The anticancer effect of hydroalcoholic extract of Aegle marmelos (AME) was studied in the Ehrlich ascites carcinoma bearing Swiss albino mice. The spatial effect of various AME administration schedules showed that six-day administration increased the survival of tumor bearing mice. The best antineoplastic action of AME was obtained when AME administered through intraperitoneal route than the oral route at equimolar dose. Administration of AME once daily for six consecutive days to the tumor bearing mice caused a dose dependent remission of the tumor at 400 mg/kg body weight, where the greatest antitumor effect was observed and the higher doses showed toxic manifestations. A 24-d lengthening in life span was observed in EAC animals treated with 400 mg/kg AME. This dose of 400 mg/kg was considered as the best dose, where the animals survived up to 43 d post-tumor-cell inoculation as against no survivors in the saline treated control group. The antitumor activity when tested for different schedules for triple administrations, the best effect was observed for 1-2-3, followed by 1-3-5 and 1-5-9 days, respectively. Stage specific evaluation of AME inhibited the increase in body weight gain in animals due to tumor development during early stages only. The AME treatment resulted in a dose dependent elevation in the median survival time (MST) and average survival time (AST) up to 400 mg/kg AME and decline thereafter. The effective dose of 400 mg of AME is 1/6th of the LD50 dose, which increased the MST and AST up to 29 and 27 d, respectively. The acute toxicity study of AME showed that the drug was non-toxic up to a dose of 1750 mg/kg b. wt. The LD10 and LD50 was found to be 2000 and 2250 mg/kg.     

萘普替尼靶向表皮生长因子受体不同突变亚型的抗肿瘤作用研究

目的 研究萘普替尼对表皮生长因子受体（EGFR）不同突变亚型荷瘤小鼠肿瘤生长的影响。方法 建立野生型EGFR人表皮鳞癌A431、L858R/T790M双突变EGFR非小细胞肺癌H1975、Del19突变型EGFR非小细胞肺癌HCC827及HER2高表达的胃癌N87的裸鼠移植瘤模型,待肿瘤长至100 mm³左右将小鼠分组,A431荷瘤小鼠分组：对照组、阿法替尼12 mg/kg和萘普替尼3.50、1.75、0.87、0.29 mg/kg;H1975荷瘤小鼠分组：对照组、阿法替尼30 mg/kg和萘普替尼7.00、3.50、1.75 mg/kg;HCC827荷瘤小鼠分组：对照组、阿法替尼12 mg/kg和萘普替尼3.50、1.75、0.87、0.60、0.29 mg/kg;N87荷瘤小鼠分组：对照组、阿法替尼12 mg/kg和萘普替尼7.00、3.50、1.75、0.87、0.29 mg/kg,每组10只动物。分组后即开始ig给药,对照组给予同体积去离子水,A431、H1975、HCC827、N87荷瘤小鼠分别给药14、21、7、14 d。观察相对肿瘤体积（RTV）、肿瘤增殖率及对肿瘤质量的抑制率,在体考察萘普替尼的抗肿瘤作用。结果 A431荷瘤小鼠：与对照组比较,萘普替尼各剂量组RTV均显著减小（P<0.01）,肿瘤增殖率分别为26.6%、32.5%、34.8%、42.2%;瘤质量均显著降低（P<0.01）,抑瘤率范围在48.3%~73.9%;0.87 mg/kg为起效剂量,3.5 mg/kg剂量与阿法替尼12 mg/kg效果相当,3.5mg/kg组小鼠体质量显著降低（P<0.01）。H1975荷瘤小鼠：与对照组比较,萘普替尼各剂量组RTV均显著降低（P<0.05、0.01）,肿瘤增殖率分别为14.5%、38.2%、65.3%;3.5 mg/kg为起效剂量,与阿法替尼30 mg/kg作用相当;7.0、3.5 mg/kg组小鼠体质量显著降低（P<0.05、0.01）。HCC827荷瘤小鼠：与对照组比较,萘普替尼3.50、1.75、0.87、0.60 mg/kg组RTV降低极为显著（P<0.01）,肿瘤增殖率均小于40%;瘤质量呈不同程度地降低,抑瘤率范围52.9%~89.7%;0.6 mg/kg为起效剂量,1.75 mg/kg剂量与阿法替尼12 mg/kg作用相当,3.5、1.75 mg/kg组小鼠体质量显著降低（P<0.01）。N87荷瘤小鼠：萘普替尼7.00、3.50、1.75 mg/kg组RTV及瘤质量均显著低于对照组（P<0.05、0.01）,且肿瘤增殖率均小于40%,抑瘤率范围54.9%~95.00%;1.75 mg/kg为起效剂量,3.5 mg/kg与阿法替尼12 mg/kg作用相当;7.0、3.5 mg/kg组小鼠体质量显著降低（P<0.01）。结论 萘普替尼具有明显的抗肿瘤作用,其中对EGFR野生型或单突变型荷瘤抗肿瘤作用较好。关键词：萘普替尼;表皮生长因子受体;表皮生长因子受体酪氨酸激酶抑制剂;突变;非小细胞肺癌     

Immunological studies on sporamycin-treated animals

Sporamycin showed a remarkable tumor regressive activity against sarcoma-180 with a single 5 mg/kg dose of intravenous administration. This antitumor effect on tumor and host animals was examined immunologically. As the results: (1) When sarcoma-180 tumor cells were used as an antigen macrophage migration inhibition reaction by spleen cells derived from the tumor-bearing mice treated with sporamycin was positive at day 7 approximately 14 after the medication and was negative thereafter. (2) The delayed hypersensitivity tested by the foot-pad reaction was positive in tumor-bearing mice treated with sporamycin, and no decrease of foot pad reaction was observed, whereas this reaction decreased remarkably in non-treated tumor-bearing mice. (3) Sarcoma-180 tumor cells were mixed with spleen cells derived from sporamycin-treated mice, and were inoculated into normal dd mice. The growth of tumor cells was inhibited markedly, but no inhibition of tumor growth was observed in case of spleen cells derived from non-treated tumor bearing mice. (4) Combined treatment of sporamycin with PS-K, an immunopotentiator, showed a remarkable synergistic effect.     

In vivo toxicity and antitumor activity of mangosteen extract

Mangosteen (Garcinia mangostana) has been widely used in the traditional medicine of Thailand to treat various ailments, especially diseases of the digestive system and infections. Many reports show antiproliferation of crude extracts and active constituents from mangosteen against many cancer cell lines. Therefore, the current study is proposed to demonstrate in vivo evidence on the antitumor activity of mangosteen. Crude methanolic extract (CME) from mangosteen pericarp including 25.19 % α-mangostin as an active xanthone was used in this study. The inhibition on tumor cell proliferation of CME was preliminarily evaluated against the murine colon cancer cell line NL-17 with an IC₅₀ value of 17 and 84 μg/ml based on WST-1 and LDH assays, respectively. The safety dose for animal application was assessed by in vivo toxicity studies using female BALB/c mice. Acute toxicity showed an LD₅₀ value and approximate lethal dose at 1,000 mg/kg, whereas the suitable dose for short-term study should be ≤200 mg/kg. The effective dose for antitumor activity of CME was found to be between 100 and 200 mg/kg, with a tumor size reduction of 50–70 %. Histological staining clearly illustrated a decrease of tumor cell density in the footpad in a dose-dependent manner. The median survival time and life span significantly increased in tumor-bearing mice with CME treatment. This study suggests that CME possesses a powerful antitumor activity. Therefore, it is worth undertaking further investigation to identify active compounds and obtain a deeper understanding of their mechanism, in order to acquire novel effective anticancer drugs.     

Resveratrol induces the suppression of tumor-derived CD4+CD25+ regulatory T cells

CD4+CD25+ regulatory T cells (Treg cells) are negative regulator of the immune system and main obstacles to cancer immunotherapy in tumor-bearing hosts. Resveratrol is a natural product found in grapes with both immunomodulatory and anticancer effects, which can be controlled by Treg cells. Therefore, to determine whether resveratrol performs these actions via Treg cells, we investigated changes in Treg cell population and immunomodulatory cytokines in EG7 tumor-bearing C57BL/6 mice. In the present study, CD4+CD25+ cell population among CD4+ cells was inhibited ex vivo by resveratrol treatment in a dose-dependent manner. FoxP3+ expressing cells among CD4+CD25+ population were significantly reduced after resveratrol treatment ex vivo in intracellular FACS analysis. Single intraperitoneal administration of 4 mg/kg resveratrol suppressed the CD4+CD25+ cell population among CD4+ cells and downregulated secretion of TGF-beta, an immunosuppressive cytokine, measured from the spleens of tumor-bearing mice. Furthermore, resveratrol enhanced IFN-gamma expression in CD8+ T cells both ex vivo and in vivo,leading to immune stimulation. Taken together, these results suggest that resveratrol has a suppressive role on CD4+CD25+ cell population and makes peritumoral microenvironment unfavorable to tumor in tumor-bearing mice. Thus, resveratrol can be considered as possible adjuvant material for vaccination-based cancer therapy.     

Characterization and antitumor activity of pollen polysaccharide

The polysaccharide LBPP was extracted and isolated from the pollen of brassica napus L., and the antitumor activity was evaluated on Sarcoma 180-bearing mice and B16 melanoma-bearing mice through transplantable animal tumor. Mice were treated with three doses of the polysaccharide LBPP (50, 100 and 200 mg/kg body weight) for 10 days. Tumor weight, relative spleen and thymus weight, lymphocyte proliferation, natural killer cell activity, delayed type hypersensitivity (DTH), phagocytic function of monocyte, serum hemolysis antibody and peripheral blood of tumor-bearing mice were studied. At the doses of 100 and 200 mg/kg, a significant decrease (P<0.01) in tumor formation, a significant increase (P<0.05) in relative spleen and thymus weight, natural killer cell activity, phagocytic function of monocyte, lymphocyte proliferation, and serum hemolysis antibody, and a significant improvement of peripheral blood abnormality (P<0.05) and anemia (P<0.01) were observed. Results of these studies demonstrated that the polysaccharide LBPP had anti-tumor activity, which was mediated by immunomodulation and leukogenic and antianemic actions.     

皖南蝮蛇毒抑瘤组分Ⅰ对人胃癌细胞SGC-7901荷瘤鼠体内抑制作用的研究

目的:研究皖南蝮蛇毒抑瘤组分Ⅰ(Agkis-trodon halys venom antitumor component Ⅰ,AHVAC-Ⅰ)对人胃癌细胞SGC-7901荷瘤鼠的体内抑制作用及瘤细胞增殖活性变化,并初步探讨其作用机制。方法:取生长状态良好的浓度为1×107个/mL的SGC-7901人胃癌细胞悬液0.1mL接种于裸小鼠右侧腋窝皮下,待其成瘤后随机分为模型组、紫杉醇阳性对照组、AH-VAC-Ⅰ高、中、低剂量组,隔日连续给药5次,定期观察肿瘤生长情况,测量肿瘤体积,绘制肿瘤生长曲线并计算抑瘤率,HE染色观察瘤体形态学变化,免疫组化SP法检测Ki-67增殖指数,原位末端标记技术(TUNEL)法检测细胞凋亡指数。结果:AHVAC-Ⅰ在1.0mg/kg剂量时对SGC-7901细胞有抑制作用,抑瘤率达42.2%;在3.0mg/kg剂量时有显著抑制作用,抑瘤率达78.5%。实验组肿瘤内Ki-67阳性细胞数量下降,凋亡细胞明显增多。结论:AHVAC-Ⅰ能明显抑制裸鼠体内SGC-7901人胃癌细胞的生长,其作用机制可能与诱导胃癌细胞发生凋亡及抑制肿瘤细胞增殖有关。