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氯喹和普萘洛尔联合治疗结直肠癌和三阴性乳腺癌的潜在作用。

Potential effect of chloroquine and propranolol combination to treat colorectal and triple-negative breast cancers.

机构信息

Instituto de Inmunología Clínica y Experimental de Rosario (IDICER, CONICET-UNR), Facultad de Ciencias Médicas (UNR), 3100, Rosario, Santa Fe, Argentina.

CONICET, Rosario, Argentina.

出版信息

Sci Rep. 2023 May 16;13(1):7923. doi: 10.1038/s41598-023-34793-6.

Abstract

Drug repositioning explores the reuse of non-cancer drugs to treat tumors. In this work, we evaluated the effect of the combination of chloroquine and propranolol on colorectal and triple-negative breast cancers. Using as in vitro models the colorectal cancer cell lines HCT116, HT29, and CT26, and as triple-negative breast cancer models the 4T1, M-406, and MDA-MB-231 cell lines, we evaluated the effect of the drugs combination on the viability, apoptosis, clonogenicity, and cellular migratory capacity. To explore the in vivo effects of the combination on tumor growth and metastasis development we employed graft models in BALB/c, nude, and CBi mice. In vitro studies showed that combined treatment decreased cell viability in a dose-dependent manner and increased apoptosis. Also, we demonstrated that these drugs act synergically and that it affects clonogenicity and migration. In vivo studies indicated that this drug combination was effective on colorectal models but only partially on breast cancer. These results contributed to the search for new and safe treatments for colorectal and triple-negative carcinomas.

摘要

药物重定位探索非癌症药物在治疗肿瘤方面的再利用。在这项工作中,我们评估了氯喹和普萘洛尔联合用于结直肠和三阴性乳腺癌的效果。使用结直肠癌细胞系 HCT116、HT29 和 CT26 作为体外模型,以及 4T1、M-406 和 MDA-MB-231 细胞系作为三阴性乳腺癌模型,我们评估了药物组合对细胞活力、细胞凋亡、集落形成和细胞迁移能力的影响。为了探索该组合对肿瘤生长和转移发展的体内影响,我们在 BALB/c、裸鼠和 CBi 小鼠中进行了移植模型研究。体外研究表明,联合治疗以剂量依赖的方式降低细胞活力并增加细胞凋亡。此外,我们证明这些药物协同作用,并影响集落形成和迁移。体内研究表明,该药物组合对结直肠模型有效,但对乳腺癌仅部分有效。这些结果有助于寻找新的、安全的结直肠和三阴性癌治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a6df/10188563/b41ccd22cf15/41598_2023_34793_Fig1_HTML.jpg

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