As_2O_3联合丹参酮ⅡA对结肠癌细胞影响分子机制的探讨

The molecular mechanism exploration of As_2O_3 combined with tanshinone ⅡA on colon cancer cells

目的探讨As_2O_3(arsenic trioxide)联合丹参酮ⅡA(TanshinoneⅡA,TanⅡA)对结肠癌细胞SW620的基质金属蛋白酶-9(MMP9)、血管内皮生长因子(VEGF)、CD44v6、nm23-H1 mRNA表达的影响,研究联合用药对结肠癌肿瘤细胞的分子作用机制。方法 SW620细胞复苏,按照干预药物不同分为空白对照组、As_2O_3单药组、TanⅡA单药组、联合用药组、阳性对照组(5-Fu组),采用实时荧光定量PCR法检测细胞中MMP9、VEGF、CD44v6、nm23-H1 mRNA表达的变化。结果与空白对照组相比,各用药组MMP9、VEGF、CD44v6的表达量显著降低(P<0.01),nm23-H1 mRNA的表达量明显增高(P<0.01);As_2O_3与TanⅡA联合用药组的MMP9、VEGF、CD44v6表达量明显低于各单药组(P<0.05),nm23-H1表达量明显上调(P<0.05)。结论 As_2O_3协同TanⅡA抑制人结肠癌SW620细胞的作用可能是通过调控MMP9、VEGF、CD44v6及nm23-H1的表达来实现的。

Objective To study the effect of arsenic trioxide（As2O3） and tanshinone ⅡA（Tan ⅡA） on the expression of matrix metallopeptidase 9（MMP9）, vascular endothelial growth factor（VEGF）, CD44 v6 and nm23-H1 m RNA in human colon cancer cell line SW620 and to study the molecular mechanism of the combined treatment on colon cancer cells. Methods The colorectal cancer SW620 cells were resuscitated and treated with As2O3 and Tan ⅡA, at the same time, the untreated SW620 cells were used as blank control, 5-fluorouracil（5-Fu） treated group was positive control group. The expression of MMP9, VEGF, CD44 v6 and nm23-H1 m RNA were detected by realtime fluorescence quantitative PCR. Results The expression levels of MMP9, VEGF, CD44 v6 m RNA in SW620 cells treated with As2O3 and Tan ⅡA were significantly lower than those in the blank control group, the single drug group and the positive control group（P〈0.01）. The expression level of nm23-H1 m RNA in SW620 cells treated with As2O3 and Tan ⅡA were significantly higher than those in the blank control group, the single drug group and the positive control group（P〈0.01）. Conclusion The inhibitory effect of As2O3 in combination with Tan ⅡA on human colon cancer SW620 cells may be through the regulation of the expression of MMP9, VEGF, CD44 v6 and nm23-H1.