三苯氧胺联合化疗对人大肠癌细胞系SW480、HT29的作用

The effects of tamoxifen combining with chemotherapy in human colorectal carcinoma cell line SW480, HT29

目的 研究三苯氧胺联合化疗药物对人结肠癌细胞系SW 4 80、HT2 9体外培养的影响及机制探讨。方法 应用MTT法 ,比较单纯用三苯氧胺和三苯氧胺与化疗药物联合对SW4 80、HT2 9细胞系生长抑制作用 ,通过化疗药物的量—效关系曲线 ,观察三苯氧胺有否化疗增敏作用 ,同时对mdr1编码产物Pgp的检测 ,探讨三苯氧胺可能的作用机制。 结果 在TAM浓度为 5 μmol/L时 ,能使SW4 80细胞系对 5 FU、MTX的敏感性分别提高 1.5 976、1.6 4 5 6倍 ;在 10 μmol/L时 ,使SW 4 80、HT2 9细胞系对 5 FU、MMC、MTX、ADM的敏感性分别提高 4 .15 2 4、2 .0 2 4 4、4 .7833、2 .2 32 3倍和 4 .7713、4 .786 5、4 .2 5 5 7、4 .4 713倍 ,差别有显著性 (P <0 .0 5 )。化疗药物使体外培养的SW 4 80、HT2 9细胞系产生耐药性 (P1,P2 <0 .0 5 ) ,TAM能显著逆转其耐药性 (P3,P4 <0 .0 5 )。结论 在体外实验中 ,一定浓度的TAM能增加人结肠癌细胞系SW 4 80、HT2 9对化疗药物 5 FU、MMC、MTX、ADM的敏感性 ,其机制可能为TAM抑制mdr1编码产物P gp的产生。

Objective To evaluate the possible effects of tamoxifen combining with chemotherapy in human colorectal carcinoma cell lines SW480、HT29. Methods Tetrazolium(MTT) assay was used and the inhibition effects were compared in cultures of SW480 and HT29 with tamoxifen alone and with tamoxifen combining with chemotherapy, and observed the possible mechanism of whether tamoxifen could increase the chemosensitization or not by detected mdrl coded P-gp.Results Tamoxifen at concentration of 5 μmol/L increased the chemosensitivity of 5-FU and MTX by 1.5976 to 1.6456-fold in SW480 cell line.Tamoxifen at concentration of 10 μmol/L increased the chemosensitivity of 5-FU、MMC、MTX、ADM by 4.1524、2.0244、4.7833 to 2.2323-fold respectively in SW480 cell line and increased 4.7713、4.7865、4.2557、4.4713-fold in HT29 cell line(P<0.05) respectively. Chemotherapy durgs caused the cultural SW480 and HT29 cell lines in vitro to produce drug resistence (P1,P2<0.05) , while Tmoxifen could significantly reverse (P3,P4<0.05).Conclusion In vitro,Tamoxifen can enhance the chemosensitivity of 5-FU、MMC、MTX、ADM at different concentrations and its possible mechanism is that Tamoxifen inhibits the increase of mdr1 mode P-gp.