洛匹那韦利托那韦联合诱导内质网应激并杀死泌尿系统癌细胞。
Lopinavir-Ritonavir Combination Induces Endoplasmic Reticulum Stress and Kills Urological Cancer Cells.
机构信息
Department of Urology, National Defense Medical College, Tokorozawa, Japan.
Department of Urology, National Defense Medical College, Tokorozawa, Japan
出版信息
Anticancer Res. 2019 Nov;39(11):5891-5901. doi: 10.21873/anticanres.13793.
BACKGROUND/AIM: Induction of endoplasmic reticulum (ER) stress is a novel approach to cancer treatment. This study investigated the ability of the clinically feasible combination of the human immunodeficiency virus protease inhibitors lopinavir and ritonavir to induce ER stress killing urological cancer cells.
MATERIALS AND METHODS
Renal cancer cells (769-P, 786-O) and bladder cancer cells (UMUC-3, T-24) were used to investigate the ability of the combination to induce ER stress and its mechanism of action.
RESULTS
The combination inhibited the growth of both renal and bladder cancer cells synergistically by inducing ER stress. The combination-induced ER stress increased the expression of AMP-activated protein kinase and suppressed the mammalian target of rapamycin pathway. It also increased the expression of a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor and thereby sensitized the cancer cells to TRAIL.
CONCLUSION
The combination of lopinavir and ritonavir acts against urological cancer cells by inducing ER stress synergistically.
背景/目的：内质网（ER）应激的诱导是一种治疗癌症的新方法。本研究探讨了临床上可行的人类免疫缺陷病毒蛋白酶抑制剂洛匹那韦和利托那韦联合应用诱导 ER 应激杀伤泌尿生殖系统癌细胞的能力。
材料和方法
使用肾癌（769-P、786-O）和膀胱癌（UMUC-3、T-24）细胞来研究联合用药诱导 ER 应激的能力及其作用机制。
结果
联合用药通过诱导 ER 应激协同抑制肾癌细胞和膀胱癌细胞的生长。联合用药诱导的 ER 应激增加了 AMP 激活的蛋白激酶的表达，抑制了哺乳动物雷帕霉素靶蛋白通路。它还增加了肿瘤坏死因子相关凋亡诱导配体（TRAIL）受体的表达，从而使癌细胞对 TRAIL 敏感。
结论
洛匹那韦和利托那韦联合作用通过协同诱导 ER 应激来抑制泌尿生殖系统癌细胞的生长。
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