人参皂苷抗结直肠癌作用机制的研究进展

人参皂苷作为人参的主要活性成分,具有诱导肿瘤细胞调亡、抑制肿瘤细胞增殖、诱导细胞周期停滞、抑制肿瘤血管生成、免疫调节、化疗增效、抗炎以及调节肠道菌群等作用。现如今,人参皂苷对结直肠癌的作用已成为研究的热点。文章就人参皂苷抗结直肠癌的作用机制进行综述。     

多糖抗辐射作用研究进展

多糖为一大类天然产物,具有能量储存、结构支持、防御和抗原决定性等多方面的生物功能,有些多糖或其衍生物还有多种药理活性,多糖已成为天然药物研究的一个热点。在研究中发现多种多糖具有明显的抗辐射作用,其机制可能与抗免疫损伤、保护造血系统、清除自由基等方面有关。本文综述了一系列多糖辐射防护实验研究结果,并对多糖辐射防护作用机制进行了初步的探讨。     

姜黄素靶向结肠癌干细胞的作用及机制研究进展

姜黄素具有广泛的抗肿瘤活性,能够抑制多种类型肿瘤的生长.近年来,有研究发现姜黄素对肿瘤干细胞,尤其是结肠癌干细胞具有直接抑制作用.然而,姜黄素影响结肠癌干细胞生存的作用机制比较复杂,可以通过调控多种信号通路、转录因子、膜受体及激酶等方式发挥效应.文章就姜黄素靶向结肠癌干细胞的作用机制研究进展进行综述,为姜黄素抗结肠癌研究提供理论依据.     

六种天然皂苷抗肿瘤作用的研究进展

目前寻找高效低毒的天然植物成分是抗癌药物研究的重要方向。天然皂苷是存在于自然界的一类复杂的苷类化合物,具有抗肿瘤、抗炎、免疫调节等广泛的药理学活性。近年报道多种皂苷具有显著的抗肿瘤活性,其抗肿瘤作用和机制在不断深入研究中,天然皂苷有望成为一类抗癌新药。     

六种天然皂苷抗肿瘤作用的研究进展

目前寻找高效低毒的天然植物成分是抗癌药物研究的重要方向。天然皂苷是存在于自然界的一类复杂的苷类化合物,具有抗肿瘤、抗炎、免疫调节等广泛的药理学活性。近年报道多种皂苷具有显著的抗肿瘤活性,其抗肿瘤作用和机制在不断深入研究中,天然皂苷有望成为一类抗癌新药。     

重楼皂苷抗肿瘤作用机制的研究进展

近年来,随着层析柱新填料的发现以及中药分离提纯技术水平的提高,重楼的化学成分以及药理作用机制等方面研究已经有了较大进展。目前认为,重楼皂苷是重楼的主要化学成分,而且已经发现重楼皂苷具有抗肿瘤、抗炎和抑制氧化应激反应等药理作用。其抗肿瘤主要作用机制包括诱导细胞凋亡、调节机体免疫功能、抑制肿瘤组织血管生长、逆转肿瘤耐药等。本文通过对国内外重楼皂苷的相关研究进行系统梳理和归纳,为明确其抗肿瘤作用机制提供参考。     

太白楤木皂苷的抗氧化作用研究

目的： 探讨太白楤木皂苷的抗氧化作用,为进一步利用其防治疾病提供基础数据。方法：采用体外化学法检测太白楤木皂苷的总抗氧化能力。在细胞实验中,采用氧化剂叔丁基过氧化氢 (tert-butyl hydroperoxide,tBHP)诱导细胞氧化损伤。设立相应对照组和药物保护组,给予太白楤木皂苷 (5 μg/mL)预处理保护,收集样品,流式细胞仪荧光法检测细胞活性氧 (reactive oxygen species,ROS)水平,Western blot方法检测抗氧化转录因子核呼吸因子2 (nuclear respiratory factor 2,Nrf2)及其下游的血红素加氧酶1 (heme oxygenase-1,HO-1)和谷氨酸半胱氨酸连接酶 (γ-glutamate-cysteine ligase,GCL)的表达水平。结果：太白楤木皂苷体外实验检测总抗氧化能力表现出明显的剂量-效应关系。在细胞实验中,tBHP可以显著提高细胞ROS水平,引起细胞的氧化损伤,太白楤木皂苷预处理可以显著降低tBHP诱导的细胞ROS水平。同时发现太白楤木皂苷可以显著拮抗tBHP引起Nrf2及其下游的HO-1、GCL 的催化亚基 (GCLC)和调节亚基 (GCLM)表达水平的升高。结论：太白楤木皂苷在化学反应体系及细胞水平,均显现出了抗氧化作用,具有抗氧化防治疾病的应用前景。     

桑黄胞内多糖的抗突变和抗氧化作用

背景与目的:探讨桑黄胞内多糖抗环磷酰胺致突变作用。材料与方法:选用小鼠50只,随机分为阴性对照组(0.86%生理盐水)、阳性对照组(环磷酰胺,CP)和桑黄胞内多糖不同剂量实验组(150、300、600mg/kg),采用小鼠骨髓嗜多染红细胞微核实验和小鼠精子畸形实验,研究桑黄液态发酵胞内多糖的抗环磷酰胺致突变作用,并检测小鼠血清和肝组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量。结果:150、300、600mg/kg剂量的桑黄胞内多糖的微核抑制率分别为24.25%、53.36%和63.43%;各剂量组精子畸形率分别为(60.33±4.16)‰、(50.00±4.08)‰、(46.75±2.98)‰,CP组为(94.80±6.49)‰,各剂量组与CP组间的差异具有统计学意义(P<0.01);桑黄胞内多糖能明显增强小鼠SOD活性,降低MDA含量;小鼠骨髓嗜多染红细胞微核率与SOD活性呈明显负相关(r血清=-0.998,r肝=-0.979,P均<0.05),与MDA含量呈明显正相关(r血清=0.997,r肝=0.989,P均<0.05)。结论:桑黄胞内多糖对由环磷酰胺引起的体细胞和生殖细胞的基因突变有着明显的拮抗作用。其机制可能与通过提高机体抗氧化防御系统的功能,防止有害自由基对细胞内生物大分子的损伤,抑制脂质过氧化的产物有关。     

大豆异黄酮抗瘤效应及其机制的研究进展

大豆异黄酮(SIF)是具有能与雌激素受体结合、诱导产生弱雌激素样作用的植物化学物质。最近的研究表明,SIF是一种很有潜力的癌症化学预防剂,对乳腺癌、结肠癌和前列腺癌、肺癌等发生具有一定的预防作用。其可能的抗瘤机制包括雌激素和抗雌激素作用、抑制酪氨酸蛋白激酶(TPK)活性、诱导癌细胞凋亡分化及与抗癌药协同作用等。     

5—FU和生物制剂联合诱导结肠癌细胞凋亡的研究

免疫治疗是抗肿瘤治疗的一个重要方面,药物治疗和免疫治疗相结合是抗肿瘤治疗的一个重要研究方向。Fas系统在结肠癌的肿瘤免疫中具有重要作用,针对Fas系统的免疫治疗可能有一定效果。本实验旨在观察治疗结肠癌的首选药物5-氟尿嘧啶(5-FU)和抗Fas单抗对结肠癌细胞株SW480的联合作用及其作用机制。     

红毛五加多糖对体外人胃癌细胞的抑制作用特点及机制

 目的　研究红毛五加多糖对胃癌细胞的抑制作用特点 ,并探讨该多糖的抑癌机制。方法　选取MTT法检测该多糖对癌细胞和正常人细胞的抑制作用特点 ,采用流式细胞仪以检测基因蛋白表达。结果　该多糖选择性地抑制胃癌细胞的活性和功能状态 ,而对正常人外周血淋巴细胞和人胚腱细胞的活性和功能状态无影响。对癌基因 c- myc蛋白表达与空白对照组比较没有显著性差异。结论　红毛五加多糖可能不是通过抑制癌基因 c- myc蛋白表达而达到抑制胃癌细胞增殖效应。由于该多糖抑制胃癌细胞的同时对健康人细胞无影响 ,故用于肿瘤的防治可能较为安全.     

Induction of macroautophagy in human colon cancer cells by soybean B-group triterpenoid saponins

The impact of triterpenoid saponins isolated from soybeans on suppression of colon cancer cell proliferation was evaluated. Experiments were conducted to determine the effects of a purified soybean B-group saponin extract on cell proliferation, cell-cycle distribution and programmed cell death in cultures of human HCT-15 colon adenocarcinoma cells. Treatment of cells with the soyasaponins at concentrations of 25-500 p.p.m. significantly reduced viable cell numbers after 24 and 48 h of exposure. Treatment of cells with 25 and 100 p.p.m. of saponins also resulted in a transient accumulation of cells in the S-phase of the cell cycle that was associated with a significant reduction of cyclin-dependant kinase-2 (CDK-2) activity. More striking was that, when examined by transmission electron microscopy, soyasaponin-treated cells exhibited an approximately 4.5-fold increase in cell morphologies characteristic of Type II non-apoptotic programmed cell death (PCD) including numerous autophagic vacuoles, changes that collectively suggest autophagic cell death. In addition, the protein levels of microtubule-associated protein light chain 3 (LC-3), a specific marker of macroautophagy, increased substantially following soyasaponin treatment. Taken together these results thus indicate that soybean saponins, at physiologically relevant doses, can suppress HCT-15 colon cancer cell proliferation through S-phase cell-cycle delay, and can induce macroautophagy, the hallmark of Type II PCD. These findings suggest that B-group soyasaponins may be another colon-cancer suppressive component of soy that warrants further examination as a potential chemopreventive phytochemical.     

多西苯醌联合塞莱昔布对结肠癌细胞转移作用的研究

目的对比研究单独及联合应用参与花生四烯酸代谢的环氧合酶-2（COX-2）及5-脂氧合酶（5-LOX）抑制剂塞来昔布与多西苯醌（AA861）代谢途径对结肠癌细胞转移的抑制作用。方法体外分组培养具有高转移能力的人类结肠癌HT-29细胞,药物分别作用48h后,采用四甲基偶氮唑盐比色（MTT）法检测AA861及塞来昔布对结肠癌细胞增殖的影响,Transwell法检测不同药物分组对结肠癌HT-29细胞迁移能力的影响,免疫荧光染色法检测细胞内细胞间黏附分子-1（ICAM-1）蛋白的变化,反转录-聚合酶链（RT-PCR）法检测细胞内ICAM-1及血管内皮生长因子（VEGF）基因表达变化。结果AA861与塞来昔布单独应用都能以时间浓度依赖性抑制结肠癌细胞增殖与迁移,其中AA861与塞莱昔布100μmol／L分别单独应用时对结肠癌细胞增殖的抑制率分别为43．2％、42．8％,两者100μmol／L联合应用时对结肠癌细胞增殖的抑制率为53．8％,与分别单独应用时比较差异有统计学意义（均P〈0．001）;AA861与塞莱昔布100μmol／L分别单独应用时对结肠癌细胞迁移的抑制率为32．0％、29．3％,两者100μmol／L联合应用时对结肠癌细胞增殖的抑制率为57．8％,与分别单独应用时比较差异有统计学意义（均P〈0．001）。免疫荧光染色及RT-PCR提示两种药物都能抑制结肠癌细胞内VEGF与ICAM-1蛋白及基因表达,小剂量联合应用都能抑制结肠癌细胞内VEGF与ICAM-1蛋白及基因表达,且两者联合应用比单独应用抑制作用强（P〈0．001）。结论小剂量塞来昔布及AA861联合应用能以协同作用抑制结肠癌细胞的增殖与迁移,其机制可能与抑制细胞内肿瘤转移相关因子VEGF及ICAM-1表达有关。     

Tocopherols and saponins derived from Argania spinosa exert, an antiproliferative effect on human prostate cancer

The aim of our study is to evaluate the antiproliferative effect of tocopherols obtained from alimentary virgin argan oil extracted from the endemic argan tree of Morocco and of saponins extracted from argan press cake on three human prostatic cell lines (DU145, LNCaP, and PC3). The results were compared to 2-methoxyestradiol as antiproliferative drug candidates. Cytotoxicity and antiproliferative effects were investigated after cells' treatment with tocopherols and saponins compared to 2-Methoxyoestradiol as the positive control. Tocopherols and saponins extracted from argan tree and 2-methoxyestradiol exhibit a dose-response cytotoxic effect and an antiproliferative action on the tested cell lines. The best antiproliferative effect of tocopherols is obtained with DU145 and LNCaP cell lines (28 μg/ml and 32 μg/ml, respectively, as GI₅₀). The saponins fraction displayed the best antiproliferative effect on the PC3 cell line with 18 μg/ml as GI₅₀. Our results confirm the antiproliferative effect of 2-methoxyestradiol and show for the first time the antiproliferative effect of tocopherols and saponins extracted from the argan tree on hormone-dependent and hormone-independent prostate cancer cell lines. These data suggest that argan oil is of potential interest in developing new strategies for prostate cancer prevention.     

Chemotherapy enhances TNF-related apoptosis-inducing ligand DISC assembly in HT29 human colon cancer cells

Cytokines such as Fas-ligand (Fas-L) and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) can induce human colon cancer cell apoptosis through engagement of their death domain receptors. All the cancer cells are not sensitive to these cytokines. We have shown recently that low doses of cytotoxic drugs could restore TRAIL-induced cell death in resistant colon cancer cell lines. The present work further explores the death pathway triggered by the cytotoxic drug/TRAIL combination in HT-29 colon cancer cells (www.alexis-corp.com). Clinically relevant concentrations of cisplatin, doxorubicin and 5-fluorouracil synergize with TRAIL to trigger HT-29 cell death. Activation of this pathway leads to apoptosis that involves both caspases and the mitochondria. An increased recruitment of Fas-associated death domain (FADD) and procaspase-8 to the TRAIL-induced death-inducing signaling complex (DISC) was shown in cells exposed to anticancer drugs. Following caspase-8 activation at the DISC level, the mitochondria-dependent death pathway is activated, as demonstrated by the cleavage of Bid, the dissipation of DeltaPsi(m), the release of mitochondrial proteins in the cytosol and the inhibitory effect of Bcl-2 expression. Importantly, besides mitochondrial potentiation, we show here that cytotoxic drugs sensitize HT-29 colon cancer cells to TRAIL-induced cell death by enhancing FADD and procaspase-8 recruitment to the DISC, a novel mechanism whose efficacy could depend partly on Bcl-2 expression level.     

Public perceptions of cancer prevention, screening, and survival: Comparison with state-of-science evidence for colon, skin, and lung cancer

Background. Lay understanding of cancer prevention, screening, and survival may influence health behavior and health outcomes. Methods. Data were from the 2005 Health Information National Trends Survey (HINTS). In our analyses, we describe population (N=5586) beliefs about cancer prevention, detection, and survival for colon, lung, and skin cancer and compare beliefs with state-of-science evidence. We examined differences by sociodemographic subgroups. Results. A majority of respondents responded consistently with state-of-science evidence in prevention for colon (78.2%), lung (81.2%), and skin cancer (83.5%). Respondents’ perceptions of screening for colon cancer were generally consistent with state-of-science evidence (89.9%); however, fewer respondents’ responded consistently with state-of-science in screening for lung (12.6%) and skin cancer (11.9%). Finally, respondents’ estimates of survival/cure of colon (66.2%) and skin cancer (63.6%) were consistent with state-of-the-science evidence in survival; however, a minority of respondents’ estimates of lung cancer survival (17.33%) were consistent with state-of-science. Sociodemographic associates of state-of-science consistent responses included younger age, greater education, and White race. Conclusions. Public knowledge of cancer prevention, screening, and survival varies by type of cancer, levels of evidence, and sociodemographic factors. These findings provide an evidence base for improving public awareness and understanding of cancer prevention, screening, and survival.     

Cytotoxic drugs up-regulate epidermal growth factor receptor (EGFR) expression in colon cancer cells and enhance their susceptibility to EGFR-targeted antibody-dependent cell-mediated-cytotoxicity (ADCC)

Cetuximab is a human–murine chimeric IgG1 monoclonal antibody to epidermal growth factor-receptor (EGFR) which exerts synergistic antitumour interactions with several cytotoxic drugs. Therefore, it is presently recommended in combination with chemotherapy in the treatment of colon, head and neck and non-small cell lung cancer. Cetuximab has been designed to inhibit EGFR signalling; however, preclinical evidence suggests that its anti-cancer effects in vivo are also related to the ability of its human IgG1 backbone to trigger immunological mechanisms. Here we have investigated whether the exposure to different cytotoxic drugs may affect the susceptibility of colon cancer cells in vitro to cetuximab immuno-targeting and related lymphokine-activated killer (LAK)-mediated antibody-dependent cell cytotoxicity (ADCC).Five colon cancer cell lines expressing a different k-ras mutational status were evaluated for: (i) EGFR-expression, (ii) susceptibility to LAK cells and (iii) cetuximab-mediated ADCC, before and after exposure to 5-flurouracil (5-FU), gemcitabine (Gem), irinotecan (Iri) alone or in multiple two/three drug combinations.These drugs were able to up-regulate EGFR expression on the surface of all the colon cancer cell lines with a maximal effect observed few hours after the exposure to GILF regimen (Gem, Iri, Levofolinic acid and 5-FU). Chemotherapy was able to greatly enhance the sensitivity to either LAK cells or cetuximab-mediated ADCC in all the colon cancer cell lines with a mechanism independent from k-ras status.The results of our study suggest that chemotherapy may enhance cetuximab-mediated immuno-targeting and ADCC thus providing the rationale to design novel immuno-biochemotherapy regimens.     

阿司匹林对人结肠癌HT-29细胞肠分化标志物表达的影响

背景与目的：非甾体抗炎药阿司匹林临床防治结肠癌确切有效,近年来有研究认为其防治结肠癌最终通过对结肠癌干细胞调控而实现。当结肠癌干细胞分化成熟时,结肠癌将不再进展、甚至消退。本研究旨在探讨非甾体抗炎药阿司匹林对人结肠癌HT-29细胞株分化的影响。方法：采用活细胞计数试剂盒CCK-8检测不同浓度阿司匹林抑制HT-29细胞增殖的作用,得出IC₅₀;采用实时荧光定量聚合酶链反应(real-time fluorescent quantitative polymerase chain reaction,RTFQ-PCR)检测阿司匹林IC₅₀干预24、48和72 h,肠分化标志物黏蛋白2(mucin 2,MUC2)、三叶因子3(trefoil factor 3,TFF3)、蔗糖酶-异麦芽糖酶(sucroseisomaltase)和溶菌酶(lysozyme)的mRNA表达情况;采用免疫细胞化学法检测MUC2蛋白在细胞中的表达情况;采用蛋白［质］印迹法(Western blot)检测sucrase-isomaltase及lysozyme的蛋白表达情况。结果：阿司匹林能明显抑制HT-29细胞的增殖,且呈时间和剂量依赖性;RTFQ-PCR和Western blot结果显示,阿司匹林干预HT-29细胞48、72 h,与对照组比较,肠杯状细胞标志物MUC2、TFF3的mRNA表达均上调(P<0.05),肠吸收细胞标志物sucrase-isomaltase和潘氏细胞标志物lysozyme的mRNA及蛋白表达均下调(P<0.05);免疫细胞化学实验结果显示,阿司匹林干预48 h,MUC2蛋白表达较对照组上调,差异有统计学意义(P<0.05)。结论：非甾体抗炎药阿司匹林能影响人结肠癌HT-29细胞肠分化标志物的表达,且可能导致其向杯状细胞表型分化。     

常用化疗药物对大肠癌细胞系PTEN蛋白表达的影响

目的　探讨常用化疗药物对大肠癌细胞系PTEN蛋白表达的调控作用。方法　采用WesternBlot法 ,检测氟脲嘧啶( 5 Fu)、丝裂霉素及顺铂作用于大肠癌细胞HT 2 96h及 2 4h后PTEN蛋白表达情况。结果　 3种药物作用 6h后 ,与对照组比较 ,PTEN表达量均呈不同程度增高 ,其中以顺铂的上升幅度最大 ,为对照组的 2 .16倍 ,5 Fu为对照组的 1.2 1倍 ,丝裂霉素为对照组的 1.5 0倍。作用 2 4h后 ,PTEN表达量顺铂为对照组的 3 .5 3倍 ,5 Fu为对照组的 1.68倍 ,丝裂霉素为对照组的 2 .2 1倍。且用上述药物作用 6h后 ,大肠癌细胞的生长速度较对照组明显减慢。结论　常用化疗药物可通过上调癌细胞中PTEN表达量来实现其抗癌作用     

Induction of apoptosis in colon cancer cells by cyclooxygenase-2 inhibitor NS398 through a cytochrome c-dependent pathway.

Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown cancer preventive activity in patients who took them frequently. These drugs can induce tumor cells to undergo apoptosis in vitro. NS398, a cyclooxygenase-2 (COX-2)-selective inhibitor, has been reported to cause apoptosis in cancer cell lines. Therefore, we examined its effect on 15 human colon cancer cell lines and investigated its mechanism of action. NS398 decreased cell viability in all of the cell lines. Tumor cells that expressed COX-2 were shown to be more sensitive to NS398 treatment. In three selected colon cancer cell lines, NS398-induced apoptosis was mediated by the release of cytochrome c from mitochondria and, consequently, by the activation of caspase-9 and caspase-3 and by the cleavage of poly(ADP-ribose) polymerase. In contrast, caspase-8 was not involved in NS398-induced apoptosis, which suggested that the cytochrome c pathway may play an important role in NS398-induced apoptosis in colon cancer cell lines. Therefore, the combination of NS398 with apoptosis-inducing drugs through cytochrome c-independent pathways may be warranted.