黄癸素对拓扑异构酶的影响及联合羟喜树碱的抗肿瘤作用

The synergistic antitumor effects of berberine α-hydroxy-β-decanoylethyl sulfonate with hydroxycamptothecine and its effect on topoisomerase

观察黄癸素联合应用羟喜树碱对肿瘤细胞的协同抑制作用,并探讨黄癸素对拓扑异构酶的影响。采用MTT法检测黄癸素联合应用羟喜树碱对体外培养肿瘤细胞增殖的抑制作用,计算IC50和联合指数(CI值)判断药物协同作用效果;通过琼脂糖凝胶电泳法测定黄癸素对SW480细胞DNA拓扑异构酶活性的影响。结果显示,与两药单用比较,黄癸素联用羟喜树碱对SW480、SGC-7901、SW1116细胞的抑制作用更显著,IC50显著降低,两药联用对各种人癌细胞株的CI值均小于1,HepG2、SW480、SGC-7901、SW1116细胞的CI值最低分别达0.447、0.626、0.161和0.178,表现为较显著的协同效果。琼脂糖凝胶电泳法结果显示,经黄癸素(2.0～8.0 mg·L-1)处理的SW480细胞拓扑异构酶Ⅰ、Ⅱ的活性均有所降低。研究表明,黄癸素可抑制拓扑异构酶的活性,与典型的TopoⅠ抑制剂羟喜树碱合用具有良好的协同抑制肿瘤细胞增殖作用,该结果可能与两药在作用机制方面的协同有关。

Synergistic antitumor effects of HB（berberine α-hydroxy-β-decanoylethyl sulfonate,houttuyn berberine） with HCPT（hydroxycamptothecine）,and its correlative mechanism were studied in vitro.MTT assay was employed to determine the cytotoxicity of HB combined with HCPT in tumor cells culture in vitro,IC50 and combination index（CI value） were used to evaluate the synergistic effects.The supercoiled DNA relaxation mediated by topoisomeraseⅠⅡ was measured by agarose gel electrophoresis assay,and influence of HB was detected.The results showed that HB could inhibit the proliferation of tumor cells（SGC-7901,SW1116 and SW480） in vitro,and the inhibition ratio was increased,IC50 was reduced when combining with HCPT.CI value of the two drugs was less than 1 in HepG2,SW480,SGC-7901 and SW1116 cells.The lowest value was 0.447,0.626,0.161 and 0.178 in these tumor cells,respectively,further indicating HB has synergistic action with HCPT on suppressing tumor proliferation.The agarose gel electrophoresis assay showed HB can inhibit topoisomeraseⅠ Ⅱ activity of SW480 cells at the concentration of 2.0-8.0 mg-L-1.HCPT is a typical inhibitor of topoisomeraseⅠ,the synergistic action between HCPT and HB on suppressing tumor proliferation is perhaps related to the congenerous inhibition of topoisomerase.