Drug resistance develops in nearly all patients with colon cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. This review provides an up-to-date summary on over-expression of ATPbinding ...Drug resistance develops in nearly all patients with colon cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. This review provides an up-to-date summary on over-expression of ATPbinding cassette(ABC) transporters and evasion of apoptosis, two representatives of transport-based and non-transport-based mechanisms of drug resistance, as well as their therapeutic strategies. Different ABC transporters were found to be up-regulated in colon cancer, which can facilitate the efflux of anticancer drugs out of cancer cells and decrease their therapeutic effects. Inhibition of ABC transporters by suppressing their protein expressions or co-administration of modulators has been proven as an effective approach to sensitize drug-resistant cancer cells to anticancer drugs in vitro. On the other hand, evasion of apoptosis observed in drug-resistant cancers also results in drug resistance to anticancer agents, especially to apoptosis inducers. Restoration of apoptotic signals by BH3 mimetics or epidermal growth factor receptor inhibitors and inhibition of cancer cell growth by alternative cell death pathways, such as autophagy, are effective means to treat such resistant cancer types. Given that the drug resistance mechanisms are different among colon cancer patients and may change even in a single patient at different stages, personalized and specific combination therapy is proposed to be more effective and safer for the reversal of drug resistance in clinics.展开更多
Objective：To investigate the cellular effects of Pien Tze Huang（片仔癀,PZH） in the HT-29 human colon carcinoma cell line.Methods：The viability of HT-29 cells was determined by MTT assay.A fluorescence-activated ce...Objective：To investigate the cellular effects of Pien Tze Huang（片仔癀,PZH） in the HT-29 human colon carcinoma cell line.Methods：The viability of HT-29 cells was determined by MTT assay.A fluorescence-activated cell sorting（FACS） analysis with annexin-V/propidium iodide（PI） and JC-1 staining were performed to determine cell apoptosis and the loss of mitochondrial membrane potential,respectively.Activation of caspase 3 was evaluated by a colorimetric assay.The mRNA expression levels of Bcl-2 and Bax were measured by reverse transcription polymerase chain reaction（RT-PCR）.Results：PZH,in a dose- and time-dependent manner,reduced viability and induced apoptosis of HT-29 cells.Moreover,PZH treatment resulted in the collapse of the mitochondrial membrane potential,activation of caspase 3,and an increase in the Bax/Bcl-2 ratio.Conclusion：PZH inhibits the growth of HT-29 cells by inducing cancer cell apoptosis via regulation of the Bcl-2 family and activation of caspase 3,which may,in part,explain its anticancer activity.展开更多
AIM:To investigate the effect of extracted soybean saponins on the growth of human colon cancer cells.METHODS:WiDr human colon cancer cells were treated with 150,300,600 or 1200 ppm of soy saponin to determine the eff...AIM:To investigate the effect of extracted soybean saponins on the growth of human colon cancer cells.METHODS:WiDr human colon cancer cells were treated with 150,300,600 or 1200 ppm of soy saponin to determine the effect on cell growth,cell morphology,alkaline phosphatase(AP) and protein kinase C(PKC) activities,and P53 protein,c-Fos and c-Jun gene expression.RESULTS:Soy saponin decreased the number of viable cells in a dose-dependent manner and suppressed 12-Otetradecanol-phorbol-13-acetate-stimulated PKC activity(P < 0.05).Cells treated with saponins developed cytoplasmic vesicles and the cell membrane became rougher and more irregular in a dose-dependent manner,and eventually disassembled.At 600 and 1200 ppm,the activity of AP was increased(P < 0.05).However,the apoptosis markers such as c-Jun and c-Fos were not significantly affected by saponin.CONCLUSION:Soy saponin may be effective in preventing colon cancer by affecting cell morphology,cell proliferation enzymes,and cell growth.展开更多
目的:探讨顺铂(顺式二氨二氯铂)(c i sdichlorodiamineplatinum,DDP)对人结肠癌Caco-2细胞凋亡及相关蛋白Bcl-2、Caspase9、Caspase3表达的影响.方法:体外培养结肠癌Caco-2细胞;检测不同浓度DDP干预下MTT染色的A值,判定其对人结肠癌细...目的:探讨顺铂(顺式二氨二氯铂)(c i sdichlorodiamineplatinum,DDP)对人结肠癌Caco-2细胞凋亡及相关蛋白Bcl-2、Caspase9、Caspase3表达的影响.方法:体外培养结肠癌Caco-2细胞;检测不同浓度DDP干预下MTT染色的A值,判定其对人结肠癌细胞恶性增殖的影响;不同浓度D D P对人结肠癌细胞凋亡的影响使用流式细胞仪进行检测,Western blot检测不同浓度DDP对人结肠癌细胞内Bcl-2蛋白的表达;应用分光光度法检测不同浓度DDP对人结肠癌细胞内Caspase9、Caspase3蛋白活性的影响.结果:(1)癌细胞增殖结果显示,在一定的作用时间范围内,Caco-2细胞存活率与DDP浓度呈负相关,具有剂量依赖性,其中4.000、2.000μg/m L干预的各组细胞抑制率最显著,差异均有统计学意义(P<0.05).而低剂量组0.250、0.125μg/m L及对照DMSO干预组细胞存活率比较差异均无统计学意义(P>0.05),其细胞存活率明显高于其他各浓度组,差异有统计学意义(P<0.01);(2)流式细胞仪检测结果显示:DDP能诱导Caco-2细胞的凋亡,其诱导凋亡的效果呈时间和剂量性依赖;(3)Western blot检测结果显示:Bcl-2蛋白在结肠癌Caco-2细胞中低表达,DDP干预Caco-2细胞72 h后,与对照组比较,Bcl-2蛋白表达明显下降(P<0.05).Caspase9、Caspase3在Caco-2细胞中低表达,DDP干预Caco-2细胞48、72 h后,与对照组比较,Caspase9、Caspase3表达明显升高(P<0.01).结论:顺铂可以抑制Caco-2细胞增殖、诱导Caco-2细胞凋亡,其机制可能与活化Caco-2细胞中Caspase9、Caspase3蛋白以及抑制Bcl-2蛋白表达有关.展开更多
文摘Drug resistance develops in nearly all patients with colon cancer, leading to a decrease in the therapeutic efficacies of anticancer agents. This review provides an up-to-date summary on over-expression of ATPbinding cassette(ABC) transporters and evasion of apoptosis, two representatives of transport-based and non-transport-based mechanisms of drug resistance, as well as their therapeutic strategies. Different ABC transporters were found to be up-regulated in colon cancer, which can facilitate the efflux of anticancer drugs out of cancer cells and decrease their therapeutic effects. Inhibition of ABC transporters by suppressing their protein expressions or co-administration of modulators has been proven as an effective approach to sensitize drug-resistant cancer cells to anticancer drugs in vitro. On the other hand, evasion of apoptosis observed in drug-resistant cancers also results in drug resistance to anticancer agents, especially to apoptosis inducers. Restoration of apoptotic signals by BH3 mimetics or epidermal growth factor receptor inhibitors and inhibition of cancer cell growth by alternative cell death pathways, such as autophagy, are effective means to treat such resistant cancer types. Given that the drug resistance mechanisms are different among colon cancer patients and may change even in a single patient at different stages, personalized and specific combination therapy is proposed to be more effective and safer for the reversal of drug resistance in clinics.
基金Supported by the National Natural Science Foundation of China(No.81073097)the Developmental Fund of CHEN Ke-ji Integrative Medicine(No.CKJ 2011001)the Natural Science Foundation of Fujian Province of China(No.2010J01195)
文摘Objective：To investigate the cellular effects of Pien Tze Huang（片仔癀,PZH） in the HT-29 human colon carcinoma cell line.Methods：The viability of HT-29 cells was determined by MTT assay.A fluorescence-activated cell sorting（FACS） analysis with annexin-V/propidium iodide（PI） and JC-1 staining were performed to determine cell apoptosis and the loss of mitochondrial membrane potential,respectively.Activation of caspase 3 was evaluated by a colorimetric assay.The mRNA expression levels of Bcl-2 and Bax were measured by reverse transcription polymerase chain reaction（RT-PCR）.Results：PZH,in a dose- and time-dependent manner,reduced viability and induced apoptosis of HT-29 cells.Moreover,PZH treatment resulted in the collapse of the mitochondrial membrane potential,activation of caspase 3,and an increase in the Bax/Bcl-2 ratio.Conclusion：PZH inhibits the growth of HT-29 cells by inducing cancer cell apoptosis via regulation of the Bcl-2 family and activation of caspase 3,which may,in part,explain its anticancer activity.
基金Supported by National Scientific Council Scientific Project Grant,No.94-2313-B-038-003
文摘AIM:To investigate the effect of extracted soybean saponins on the growth of human colon cancer cells.METHODS:WiDr human colon cancer cells were treated with 150,300,600 or 1200 ppm of soy saponin to determine the effect on cell growth,cell morphology,alkaline phosphatase(AP) and protein kinase C(PKC) activities,and P53 protein,c-Fos and c-Jun gene expression.RESULTS:Soy saponin decreased the number of viable cells in a dose-dependent manner and suppressed 12-Otetradecanol-phorbol-13-acetate-stimulated PKC activity(P < 0.05).Cells treated with saponins developed cytoplasmic vesicles and the cell membrane became rougher and more irregular in a dose-dependent manner,and eventually disassembled.At 600 and 1200 ppm,the activity of AP was increased(P < 0.05).However,the apoptosis markers such as c-Jun and c-Fos were not significantly affected by saponin.CONCLUSION:Soy saponin may be effective in preventing colon cancer by affecting cell morphology,cell proliferation enzymes,and cell growth.
