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p53通路在细胞周期停滞和细胞凋亡中起重要作用.p53的下降可增加肿瘤细胞对化疗或放疗的耐药性.小鼠双微蛋白2(murine double minute2,MDM2)可与p53结合,调节其转录活性和稳定性.本研究旨在观察MDM2拮抗剂Nutlin-3a在非小细胞肺癌野生型p53+/+A549细胞及p53-/-H1299细胞对紫杉醇的反应中的作用.研究发现,Nutlin-3a联合紫杉醇可使A549细胞G0-G1和G2-M期明显增多,S期显著减少;凋亡百分率显著低于单紫杉醇处理组与p53-/-的H1299细胞组.总之,Nutlin-3a联合紫杉醇大大减少了野生型p53+/+的A549细胞对紫杉醇的敏感性,Nutlin-3a对紫杉醇毒性的调控依赖于p53的状态,它可以保护野生型p53细胞免受有丝分裂抑制药物紫杉醇的杀伤.
p53 pathway plays an important role in cell cycle arrest and apoptosis.P53 decline can increase the resistance of tumor cells to chemotherapy or radiotherapy.Mouseine 2 (MDM2) can bind to p53 and regulate Its transcriptional activity and stability.The purpose of this study was to investigate the role of MDM2 antagonist Nutlin-3a in the response of paclitaxel to wild-type p53 + / + A549 cells and p53 - / - H1299 cells in non-small cell lung cancer.It was found that Nutlin- 3a combined with paclitaxel significantly increased the number of G0-G1 and G2-M phases and significantly reduced the number of S phase in A549 cells, and the percentage of apoptotic cells was significantly lower than that of H1299 cells treated with paclitaxel alone and p53 - / -. In conclusion, Nutlin-3a combined with paclitaxel Greatly reduces the sensitivity of wild-type p53 + / + A549 cells to paclitaxel. The regulation of paclitaxel’s toxicity by Nutlin-3a depends on the state of p53, which can protect the wild-type p53 cells from the mitotic inhibitor paclitaxel.