Qu Kai, Lin Ting, Wang Zhixin, Liu Sinan, Chang Hulin, Xu Xinsen, Meng Fandi, Zhou Lei, Wei Jichao, Tai Minghui, Dong Yafeng, Liu Chang
Department of Hepatobiliary Surgery, Xi'an Jiaotong University, Xi'an, 710061, China.
Front Med. 2014 Jun;8(2):227-35. doi: 10.1007/s11684-014-0327-1. Epub 2014 Apr 22.
Accelerated senescence is important because this process is involved in tumor suppression and has been induced by many chemotherapeutic agents. The platinum-based chemotherapeutic agent cisplatin displays a wide range of antitumor activities. However, the molecular mechanism of cisplatin-induced accelerated senescence in hepatocellular carcinoma (HCC) remains unclear. In the present study, the growth inhibitory effect of cisplatin on HepG2 and SMMC-7721 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cellular senescence was then assessed by β-galactosidase assay. Senescence-related factors, including p53, p21, and p16, were evaluated by quantitative reverse transcription-polymerase chain reaction. Reactive oxygen species (ROS) was analyzed by flow cytometry. Our results revealed that cisplatin reduced the proliferation of HepG2 and SMMC-7721 cells in a dose- and time-dependent manner. Senescent phenotype observed in cisplatintreated hepatoma cells was dependent on p53 and p21 activation but not on p16 activation. Furthermore, cisplatininduced accelerated senescence depended on intracellular ROS generation. The ROS scavenger N-acetyl-L-cysteine also significantly suppressed the cisplatin-induced senescence of HepG2 and SMMC-7721 cells. In conclusion, our results revealed a functional link between intracellular ROS generation and cisplatin-induced accelerated senescence, and this link may be used as a potential target of HCC.
细胞加速衰老很重要，因为这个过程参与肿瘤抑制，并且已被多种化疗药物诱导。铂类化疗药物顺铂具有广泛的抗肿瘤活性。然而，顺铂诱导肝细胞癌（HCC）细胞加速衰老的分子机制仍不清楚。在本研究中，通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法检测顺铂对HepG2和SMMC-7721细胞的生长抑制作用。然后通过β-半乳糖苷酶法评估细胞衰老情况。通过定量逆转录-聚合酶链反应评估衰老相关因子，包括p53、p21和p16。通过流式细胞术分析活性氧（ROS）。我们的结果显示，顺铂以剂量和时间依赖性方式降低HepG2和SMMC-7721细胞的增殖。在顺铂处理的肝癌细胞中观察到的衰老表型依赖于p53和p21的激活，而不依赖于p16的激活。此外，顺铂诱导的加速衰老依赖于细胞内ROS的产生。ROS清除剂N-乙酰-L-半胱氨酸也显著抑制顺铂诱导的HepG2和SMMC-7721细胞衰老。总之，我们的结果揭示了细胞内ROS产生与顺铂诱导的加速衰老之间的功能联系，并且这种联系可能作为HCC的潜在靶点。
