顺铂联合siRNA干扰CD147基因抗肝癌效果体外研究

RNAi-mediated silencing of CD147 increases the anticancer effects of cisplatin on cell proliferation, death and invasion in human hepatoma cells in vitro

目的探讨化疗药物联合应用RNA干扰技术对体外肝癌细胞生长和侵袭能力的抑制作用。方法利用小片段干扰RNA(si RNA)干扰肝癌SMMC7721、Hep G2及HCC7402细胞CD147基因表达,观察沉默CD147基因增强顺铂对肝癌细胞活力、细胞死亡及侵袭能力的影响。结果沉默CD147基因能显著增强顺铂对肝癌细胞活力的抑制,si RNA-CD147联合顺铂处理组与顺铂处理组SMMC7721细胞生长抑制率分别为62.90%、37.08%(P<0.01);能显著促进肝癌细胞死亡,si RNA-CD147联合顺铂处理组与顺铂处理组SMMC7721细胞死亡率分别为(57±3)%、(45±3)%(P<0.05);同时也能显著增强顺铂对肝癌细胞侵袭能力的抑制作用,si RNA-CD147联合顺铂处理组与顺铂处理组SMMC7721细胞穿膜细胞数分别为14.5±2.3、29±2.5(P<0.01)。结论 si RNA沉默肝癌细胞CD147基因能增强肝癌细胞对顺铂的敏感性,该联合疗法为肝癌的综合治疗提供了新的思路和方法。

Objective To investigate the synergistic anticancer effects of cisplatin combined with down-regulation of CD147 by small interference RNA （siRNA） on human hepatoeellular carcinoma （HCC） cells in vitro. Methods Specific siRNA targeting CD147 （siRNA-CD147） was transfected into HCC cells SMMC7721, HepG2 and HCC7402 and CD147 expression was detected by Western blot. Cell proliferation, death and invasive potential were determined by MTT assay, Trypan blue exclusion assay and transwell invasion assay, respectively. Results Specific siRNA-CD147 dominantly down-regulated CD147 protein expression in all three HCC cell lines. MTT assays showed that siRNA-CD 147 plus cisplatin significantly increased the cell viability inhibition in SMMC7721 cells as compared with that in SMMC7721 cells treated with cisplatin （62.9% vs 37.08%, P 〈 0.01）. Trypan blue exclusion assays showed that the ratio of cell death in SMMC7721 cells treated with siRNA-CD147 plus cisplatin and cisplatin was （57± 3）% and （45 ± 3）% （P 〈 0.05）. Transwell invasion assays showed that siRNA-CD147 plus cisplatin significantly decreased the number of invaded SMMC7721 cells, as compared with cisplatin group （29 ± 2.5, 14.5 ± 2.3, P 〈 0.01）. Conclusion Specific siRNA-CD147 increases chemosensitivity to cisplatin in HCC cells in vitro. The combination of cisplatin and specific siRNA-CD147 may be a potential therapeutic strategy for HCC.