Zhang Hongming, Chen Runzhe, Wang Xiyong, Zhang Haijun, Zhu Xiaoli, Chen Jibei
Department of Respiratory Medicine, The Affiliated Yancheng Hospital, Medical School, Southeast University, Yancheng, China.
Department of Hematology and Oncology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China.
Front Oncol. 2019 Jul 24;9:538. doi: 10.3389/fonc.2019.00538. eCollection 2019.
Platinum-based chemotherapy is recommended as the first-line treatment regimen for patients with advanced non-small-cell lung cancer (NSCLC). Lobaplatin (LBP), a third-generation platinum anti-neoplastic agent, has shown an improved efficacy. This study is aimed to investigate the mechanisms of LBP-induced apoptosis in the A549 p53 wild-type cell line. The Cell Counting Kit-8 assay (CCK-8), flow cytometry (FCM), Western blot, xenograft tumor models, terminal deoxynucleotide transferase dUTP nick end labeling (TUNEL), and RNA interference were used in this study. Our results showed that the proliferation of A549 cells could be inhibited by LBP. At lower concentrations, LBP triggered cell cycle arrest at the G1 phase in A549 cells. LBP could also induce apoptosis of A549 cells. LBP also increased the expression of PARP and Bax and the cleavage of caspase-3, caspase-8, and caspase-9 and reduced Bcl-2 expression. experiment confirmed that LBP could inhibit tumor growth in the A549 xenograft models and induce apoptosis. Apoptosis of A549 cells was decreased after transfected with p53 shRNA or treated with reactive oxygen species inhibitor NAC and p38MAPK inhibitor SB203580, suggesting that the p53/ROS/p38MAPK pathway appeared to mediate the LBP-induced apoptosis of A549 cells. Our data demonstrate that LBP could be a promising candidate for the treatment of NSCLC with wild-type p53.
铂类化疗被推荐作为晚期非小细胞肺癌（NSCLC）患者的一线治疗方案。洛铂（LBP），一种第三代铂类抗肿瘤药物，已显示出更高的疗效。本研究旨在探讨LBP诱导A549 p53野生型细胞系凋亡的机制。本研究采用细胞计数试剂盒-8法（CCK-8）、流式细胞术（FCM）、蛋白质免疫印迹法、异种移植瘤模型、末端脱氧核苷酸转移酶dUTP缺口末端标记法（TUNEL）和RNA干扰技术。我们的结果表明，LBP可抑制A549细胞的增殖。在较低浓度下，LBP可使A549细胞的细胞周期阻滞于G1期。LBP还可诱导A549细胞凋亡。LBP还可增加PARP和Bax的表达以及caspase-3、caspase-8和caspase-9的裂解，并降低Bcl-2的表达。实验证实，LBP可抑制A549异种移植模型中的肿瘤生长并诱导凋亡。用p53 shRNA转染或用活性氧抑制剂NAC和p38丝裂原活化蛋白激酶抑制剂SB203580处理后，A549细胞的凋亡减少，提示p53/ROS/p38丝裂原活化蛋白激酶途径似乎介导了LBP诱导的A549细胞凋亡。我们的数据表明，LBP可能是治疗p53野生型NSCLC的一个有前景的候选药物。
