Xiong Ying, Zhao QiuYu, Gu LiYan, Liu ChunYing, Wang Chun
Basic Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Minimally Invasive Diagnosis and Treatment Section, The Fourth Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, China.
Evid Based Complement Alternat Med. 2018 Oct 16;2018:8258246. doi: 10.1155/2018/8258246. eCollection 2018.
The goal of this evaluation was to examine the mechanisms of Shenqi Fuzheng injection (SFI), an extract made from the plants and , in the process of chemotherapy sensitivity in non-small-cell lung cancer (NSCLC) cells. We investigated the expression of mitofusin-2 (Mfn2), a mitochondrial GTPase that may be related to chemoresistance, and found that Mfn2 expression was lower in human cisplatin-resistant lung carcinoma A549/DDP cells than in cisplatin-susceptible A549 cells. Chemosensitivity to cisplatin was restored in A549/DDP cells following supplementation in conjunction with SFI treatment, the effect of which we evaluated cell cycle, apoptosis, and cell signaling analysis. We found that the combined use of A549/DDP cells with SFI and cisplatin enhanced cell cycle arrested in the G/M phase, which was accompanied by upregulation of p53 and p21 protein expression and induced mitochondrial apoptosis in conjunction with the upregulation of Bax and the downregulation of Bcl-2 protein expression. Moreover, cell cycle arrest and mitochondrial apoptosis coincided with the upregulation of Mfn2 expression, which, in turn, was related to the increased mitochondrial membrane permeabilization and elevated reactive oxygen species. In summary, our findings suggest that the effect of SFI in increasing chemotherapy sensitivity in cisplatin resistance of NSCLCs occurs through cell cycle arrest and the initiation of mitochondrial apoptosis involved in the upregulation of Mfn2 expression.
本评估的目的是研究参芪扶正注射液（SFI）（一种从[植物名称1]和[植物名称2]中提取的提取物）在非小细胞肺癌（NSCLC）细胞化疗敏感性过程中的作用机制。我们研究了与化疗耐药性可能相关的线粒体GTP酶——线粒体融合蛋白2（Mfn2）的表达，发现人顺铂耐药肺癌A549/DDP细胞中的Mfn2表达低于顺铂敏感的A549细胞。在A549/DDP细胞中联合补充SFI治疗后，其对顺铂的化疗敏感性得以恢复，我们通过细胞周期、凋亡及细胞信号分析对其效果进行了评估。我们发现，A549/DDP细胞与SFI及顺铂联合使用可增强细胞周期阻滞于G/M期，这伴随着p53和p21蛋白表达上调，并通过上调Bax及下调Bcl-2蛋白表达诱导线粒体凋亡。此外，细胞周期阻滞和线粒体凋亡与Mfn2表达上调同时出现，而Mfn2表达上调又与线粒体膜通透性增加及活性氧水平升高有关。总之，我们的研究结果表明，SFI增加NSCLC顺铂耐药化疗敏感性的作用是通过细胞周期阻滞及启动与Mfn2表达上调有关的线粒体凋亡实现的。
