Department of Radiation Oncology, Liaocheng People's Hospital, Liaocheng, Shandong, China.
Department of Radiation Oncology, Liaocheng Cancer Hospital, No 45 Jianshe East Road, Liaocheng, Shandong, 252000, China.
Ther Adv Respir Dis. 2019 Jan-Dec;13:1753466619866097. doi: 10.1177/1753466619866097.
Clinical treatment of non-small cell lung carcinoma (NSCLC) by cisplatin eventually results in drug resistance, which cancer stem cells and autophagy are believed to be involved in. In the present study, we aimed to explore the effect of autophagy-inhibited cancer stem cells in NSCLC.
Cancer stem cells were identified by CD133 expression levels detected by immunochemistry, real-time polymerase chain reaction, western blot, and flow cytometry. Stemness was detected by sphere-forming assays of tumor cells. Autophagy was determined by LC3-II expression at mRNA and protein levels. The effect of chloroquine (CQ) on autophagy was detected by real-time polymerase chain reaction, western blot and sphere-forming assay , and tumor growth in male NOD/SCID mice.
Cisplatin (CDDP) treatment enhanced CD133 cell ratios in clinical NSCLC specimens and NSCLC cell line A549. The CD133 cells enriched by CDDP exhibited higher autophagy levels. Autophagy inhibition by CQ inhibited CD133 stemness and promoted CDDP efficiency in A549 cells. In addition, the combination of CDDP and CQ treatment significantly inhibited autophagy levels and cancer stem cell proportions , and dramatically suppressed tumor growth compared with individual agents.
Autophagy inhibition of cancer stem cells could promote the efficacy of cisplatin against NSCLC.
顺铂治疗非小细胞肺癌（NSCLC）最终会导致耐药，这被认为与癌症干细胞和自噬有关。在本研究中，我们旨在探讨自噬抑制的癌症干细胞对 NSCLC 的影响。
通过免疫化学、实时聚合酶链反应、western blot 和流式细胞术检测 CD133 表达水平来鉴定癌症干细胞。通过肿瘤细胞的球体形成实验检测干性。通过 LC3-II 在 mRNA 和蛋白质水平上的表达来确定自噬。通过实时聚合酶链反应、western blot 和球体形成实验检测氯喹（CQ）对自噬的影响，并检测其在雄性 NOD/SCID 小鼠中的肿瘤生长情况。
顺铂（CDDP）处理增强了临床 NSCLC 标本和 NSCLC 细胞系 A549 中 CD133 细胞的比例。CDDP 富集的 CD133 细胞表现出更高的自噬水平。CQ 抑制自噬抑制了 A549 细胞中的 CD133 干性，并增强了 CDDP 的疗效。此外，与单独用药相比，CDDP 和 CQ 联合治疗显著抑制了自噬水平和癌症干细胞比例，并显著抑制了肿瘤生长。
癌症干细胞的自噬抑制可增强顺铂对 NSCLC 的疗效。
