顺铂联合唑来膦酸对肺癌A549细胞增殖的影响及其机制

Mechanism of cisplatin combined with zoledronic acid on lung cancer A549 cells

目的观察顺铂联合唑来膦酸对肺癌A-549细胞增殖的影响并探讨其作用机制。方法以噻唑蓝（MTT）比色法观察顺铂联合唑来膦酸对A549细胞增殖的影响，以Annexin-V／PI双染法检测细胞凋亡，逆转录一聚合酶链反应（RT—PcR）检测DNA损伤检查点蛋白调节因子1（MDCl）mRNA的表达。结果顺铂联合唑来膦酸对A549细胞增殖的抑制率（39．16±4．94）％高于顺铂（16．87±2．50）％、唑来膦酸（19．66±4．57）％；联合用药诱导A549细胞的凋亡率（32．30±0．50）％较顺铂（23．90±2．46）％、唑来膦酸（18．87±3．04）％上升；联合用药后A549细胞MDC1 mRNA的相对表达水平（0．134±0．037）较顺铂（0．356±0．033）、唑来膦酸（0．208±0.040）下降，差异均有统计学意义（P〈0．05）。结论顺铂、唑来膦酸可抑制肺癌A549细胞的增殖，诱导其凋亡；顺铂联合唑来膦酸抑制A549细胞的增殖具有协同作用；其协同作用可能与下调MDC1 mRNA表达有关。

Objective To investigate the function of cisplatin combined with Zoledronic acid on proliferation and mechanisms of A549 cells. Methods （ 1 ） Methyl thiazol tetrazolium （MTr） assay and Annexin V-FITC/PI double-staining flow cytometry were employed to observe the effects of cisplatin combined with Zoledronic acid upon anti-proliferation and apoptosis respectively. Reverse transcription-polymerase chain reaction （RT-PCR） was applied to assay mRNA expression of MDC1 among different groups. Results Inhibition of the cell proliferation was observed under the treatment of combined cisplatin and zoledronic acid （39. 16 ±4.94） %, superior to the treatment of zoledronic acid （ 19.66 ±4. 57） % or cisplatin （ 16. 87 ± 2. 50） %. Combined group induced A549 cells apoptosis （32. 30 ±0. 50） %, compared with cisplatin （23.90 ±2. 46）%, zoledronic acid （18.87 ± 3.04 ）%, the difference was statistically significant ;cisplatin after zoledronic acid treatment of A549 cells MDC1 mRNA expression （0. 134 ±0. 037 ） was significantly decreased compared with single-drug, zoledronic acid （0. 208 ± 0. 040 ）and cisplatin （0. 356 ±0. 033） （P 〈 0.05 ）. Conclusion Zoledronic acid or cisplatin can significantly inhibit A549 cell proliferation and markedly induce the apoptosis. Zoledronic acid and cisplatin in a synergistic way inhibited the cell proliferation and induced apoptosis on A549 cell. The downregulated expression level of MDC1 mRNA may involved in the mechanism of synergistic effect.