An Qi, Han Chao, Zhou Yubing, Li Feng, Li Duolu, Zhang Xiaojian, Yu Zujiang, Duan Zhenfeng, Kan Quancheng
Department of Clinical Pharmacology, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, China.
Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University Zhengzhou 450052, China.
Int J Clin Exp Med. 2015 Nov 15;8(11):20516-23. eCollection 2015.
Non-small-cell lung cancer (NSCLC) is the leading cause of death from cancer in the United States. Chemotherapy prolongs survival among patients with advanced disease, but at the cost of clinically significant adverse effects. As a novel promising oncotherapy method, induced differentiation by mitomycin C has been applied for NSCLC therapy at recent year. In this study, the molecular mechanism of differentiation interruption by mitomycin C in the NSCLC line A549 was investigated. High dosage of mitomycin C (300 µM) could significantly inhibit cell proliferation (P < 0.05) by 48.39 ± 3.32% (P < 0.05), under which cell shrinkage and disruption were observed. Flow cytometry assay showed that the proportion of G1/G0 cells significantly increased, while that of S and G2/M cells significantly decreased after treatment of mitomycin C (10 or 300 µM) for 24 h. These results indicated that cell arrest by mitomycin C appeared. Additionally, up-regulation of retinoblastoma (Rb) gene by low concentration of mitomycin C (10 µM) was detected using immunohistochemistry (IHC) and Western blot assay, indicating a role in the regulation of cell cycle inhibition of this cell line.
非小细胞肺癌(NSCLC)是美国癌症死亡的主要原因。化疗可延长晚期疾病患者的生存期,但代价是产生具有临床意义的不良反应。作为一种有前景的新型肿瘤治疗方法,近年来丝裂霉素C诱导分化已应用于NSCLC治疗。在本研究中,对丝裂霉素C在NSCLC细胞系A549中中断分化的分子机制进行了研究。高剂量丝裂霉素C(300 µM)可显著抑制细胞增殖(P < 0.05),抑制率为48.39 ± 3.32%(P < 0.05),在此剂量下可观察到细胞萎缩和破裂。流式细胞术检测显示,用丝裂霉素C(10或300 µM)处理24小时后,G1/G0期细胞比例显著增加,而S期和G2/M期细胞比例显著降低。这些结果表明丝裂霉素C导致了细胞停滞。此外,使用免疫组织化学(IHC)和蛋白质印迹分析检测到低浓度丝裂霉素C(10 µM)可上调视网膜母细胞瘤(Rb)基因,表明其在调节该细胞系细胞周期抑制中发挥作用。