Background/Aim: Nelfinavir is a human immunodeficiency virus protease inhibitor that is currently being repositioned as an anticancer drug. Chloroquine, an anti-malarial lysosomotropic drug, inhibits autophagy. It has been reported that the combination of nelfinavir and chloroquine significantly enhances endoplasmic reticulum (ER) stress and induces selective cell death in multiple cell line models (in vitro). Materials and Methods: We assessed the effects of the combination of these drugs on human NSCLC cell lines in vitro using cell proliferation assay and performed preclinical treatment studies using cell line-derived xenograft mouse models in vivo. Results: In vitro, this combination enhanced inhibition of NSCLC cell proliferation with increased proteotoxicity, including ER stress, and apoptosis. In vivo, the growth of human NSCLC xenograft tumors was inhibited, which correlated with increased apoptosis and induction of ER stress as well as NSCLC growth in vitro. Conclusion: Our findings suggest that the induction of proteotoxicity provides a promising new target for developing anticancer drugs.

中文翻译：

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将奈非那韦与氯喹结合使用可抑制人肺癌异种移植肿瘤的体内生长

背景/目的：奈非那韦是一种人类免疫缺陷病毒蛋白酶抑制剂，目前正在重新定位为抗癌药物。氯喹是一种抗疟疾溶酶体药物，可抑制自噬。据报道，奈非那韦和氯喹的组合可显着增强内质网 (ER) 应激，并在多个细胞系模型（体外）中诱导选择性细胞死亡。材料和方法：我们使用细胞增殖试验在体外评估了这些药物的组合对人 NSCLC 细胞系的影响，并在体内使用细胞系衍生的异种移植小鼠模型进行了临床前治疗研究。结果：在体外，这种组合增强了对 NSCLC 细胞增殖的抑制，并增加了蛋白毒性，包括内质网应激和细胞凋亡。体内，人 NSCLC 异种移植肿瘤的生长受到抑制，这与细胞凋亡增加和 ER 应激的诱导以及 NSCLC 体外生长相关。结论：我们的研究结果表明蛋白毒性的诱导为开发抗癌药物提供了一个有希望的新靶点。