PJ34对多发性骨髓瘤RPMI8226细胞体外生长及其对马法兰敏感性的影响

Effects and mechanism of PJ34 and melphalan on human multiple myeloma cell line RPMI8226

目的:观察PJ34对多发性骨髓瘤细胞株RPMI8226体外生长的影响以及与小剂量马法兰的协同作用,初步探讨其作用机制。方法:采用MTT法检测细胞增殖抑制率,Western blot方法检测FA/BRCA途径中的相关蛋白表达、流式细胞仪测定细胞周期及凋亡率。结果:PJ34能使细胞发生G2/M期阻滞、协同马法兰诱导细胞凋亡作用。PJ34与马法兰联用与单用马法兰相比,细胞凋亡率由(31.08±0.47)%增至(45.38±4.53)%。PJ34介导的FA/BRCA途径相关因子受抑制及γH2AX表达增强,从而抑制DNA的损伤修复。结论:PJ34对多发性骨髓瘤RPMI8226细胞有显著的抑制作用,并可增加RPMI8226细胞对烷化剂类化疗药物马法兰的敏感性,其作用机制可能是通过抑制FA/BRCA途径对DNA损伤的修复。PJ34与小剂量烷化剂化疗药物合用,是一种安全有效的逆转耐药的治疗方案。

Objective：To observe the effects of PJ34 on MM cell line RPMI8226 and the synergetie effect with small doses of melphalan, and to explore its meehanisim. Methods：The inhibitory effects of the drugs on the growth of RPMI8226 cells were determined by MTT assay. The expression of FA/BRCA pathway related genes was determined by Western blot. Cell cycle phase was analysed by flow cytometry. Results： PJ34 - mediated inhibition of the related genes involved in FA/BRCA pathway and the enhanced expression of γH2AX gene,thereby inhibiting the DNA dam- age repair. P J34 can make cells have G2/M phase arrest,collaborate melphalan to induce cell apoptosis. The apoptosis percentage of RPMI8226 cells was significantly increased from （31.08± 0.47） % to （45.38 ± 4.53） % by the treat- ment of melphalan plus P J34. Conclusion： PJ34 can significantly inhibit human multiple myeloma cell line RP- Mi8226,and increase the sensitivity of RPMI8226 cells to alkylating agent chemotherapy drug melphalan,the inhibi- tion of FA/BRCA pathway may be the mechanism. PJ34 may be a safe reversal agent of drug resistance with low - dose alkylating agents.