miR-99a模拟物提高膀胱癌细胞化疗药物敏感性的机制研究

miR-99a mimics improve the bladder cancer cell sensitivity to chemotherapeutic drugs:the mechanism research

目的:研究miR-99a模拟物对膀胱癌细胞增殖及化疗药物敏感性的影响及相关分子机制。方法:培养膀胱癌BIU-87细胞株,随机分为对照组、吡柔比星组、miR-99a组、吡柔比星+miR-99a组,分别采用不含血清的培养基、1.0μg/mL的吡柔比星、miR-99a的模拟物以及miR-99a的模拟物联合1.0μg/mL的吡柔比星进行处理,处理后12、24、48h时分别测定细胞活力以及PI3K、AKT、ABCE1、MRPS5的表达量。结果:吡柔比星组、miR-99a组、吡柔比星+miR-99a组的细胞活力值以及PI3K、AKT、ABCE1、MRPS5的表达量均显著低于对照组,吡柔比星+miR-99a组的细胞活力值以及PI3K、AKT、ABCE1、MRPS5的表达量均显著低于吡柔比星组和miR-99a组。结论:miR-99a模拟物能够通过靶向抑制PI3K/AKT信号通路及下游ABCE1、MRPS5基因表达的方式抑制膀胱癌细胞增殖、增加膀胱癌细胞对化疗药物的敏感性。

Objective： To study the effects of miR-99a mimics on bladder cancer cell proliferation and sensitivity to che- motherapeutic drugs as well as the related molecular mechanisms. Methods： BIU-87 bladder cancer cell lines were cultured and randomly divided into control group, pirarubicin group, miR-99a group and pirarubicin ＋miR-99a group that were treated with culture medium without serum, 1.0 μg/mL pirarubicin, miR-99a mimics and miR-99a mimics combined with 1.0 μg/mL pirarubicin respectively, and after 12h, 24h and 48h of treatment, the cell viability as well as the expression of PI3K, AKT, ABCE1 and MRPS5 were determined respectively. Results： Cell viability values as well as the expression levels of PI3K, AKT, ABCE1 and MRPS5 of pirarubicin group, miR-99a group and pirarubicin ＋ miR-99a group were significantly lower than those of control group, and cell viability value as well as the expression levels of PI3K, AKT, ABCE1 and MRPS5 of pirarubicin ＋ miR-99a group were significantly lower than those of pirarubicin group and miR-99a group. Conclusion： miR-99a mimics can in- hibit bladder cancer cell proliferation and increase the sensitivity of bladder cancer cells to chemotherapeutic drugs through tar- geted inhibition of PI3K/AKT signaling pathway and downstream ABCE1 and MRPS5 gene expression.