目的 探讨抑制PAR4表达对肠癌细胞SW620药敏性的影响.方法 采用MTT法测定SW620细胞、空载体转染细胞SW620/pcDNA3.1(+)和针对人PAR4的人工microRNA表达载体转染细胞SW620-ml、SW620-m2对肠癌临床常用化疗药物5-氟尿嘧啶和顺铂的IC50,分析抑制PAR4的表达对SW620细胞药物敏感性的影响.结果 与SW620和SW620/pcDNA3.1(+)两组对照细胞相比,PAR4表达受抑制的SW620-ml、 SW620-m2两组细胞对5-氟尿嘧啶的IC50均显著升高(p<0.01),对顺铂的IC50亦有明显升高(P<0.01,P<0.05).结论 抑制肠癌SW620细胞PAR4的表达将增加其对5-氟尿嘧啶和顺铂的耐受,提示以PAR4为靶点的肠癌联合药物治疗研究需要综合考虑用药的合理性.
Objective To explore the effect of PAR4 inhibition on sensitivity to chemotherapeutic drugs of human colorectal carcinoma SW620 cells. Methods MTT method was used to determine the half-inhibition concentration ( IC50 ) to chemotherapeutic drugs that are commonly used in clinical treatment of colorectal cancer 5-Fu and DDP for human colorectal carcinoma SW620 cells, vector-alone transfected SW620 cells and PAR4- targeting artificial microRNA-expressing vector transfected SW620-ml and SW620-m2 cells. Results Compared with parental cell line SW620 and vector control SW620/pcDNA3.1 ( + ) cells, the SW620-m 1 and SW620-m2 cell line with inhibited PAR4 expression exhibited significantly increased IC50 for 5-Fu ( P〈0.01 ) and DDP ( P〈0.01, P〈0105 ) . Conclusions Inhibition of PAR4 expression in SW620 cells leads to the increase of drug resistance to 5-Fu and cisplatin, which suggests that reasonableness should be considered when conducting investigation on combination of PAR4- targeting therapy with other chemotherapeutic drugs for colorectal cancer treatment.