Repurposing of atorvastatin and metformin denotes their individual and combined antiproliferative effects in non-small cell lung cancer

IF 2.1 4区 医学 Q3 PHARMACOLOGY & PHARMACY Fundamental & Clinical Pharmacology Pub Date : 2024-01-23 DOI:10.1111/fcp.12981
Elsayed I. Salim, Safaa Elsebakhy, Mohamed Hessien
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引用次数: 0

Abstract

Background

Due to the limited success in the treatment of lung adenocarcinomas, new treatment protocols are urgently needed to increase the curability rate and the survival of lung cancer patients.

Objectives

Although statins, like atorvastatin (Ator), and metformin (Met) are widely accepted as hypolipidemic and hypoglycemic drugs, respectively, there are many predictions about their enhancing antitumor effect when they are combined with traditional chemotherapeutics.

Methods

The individual and combined antiproliferative potential of Ator and Met was tested by MTT-assay in non-small cell lung cancer (NSCLC) A549 cell line, compared to the corresponding effect of Gemcitabine (Gem) with implication on the mechanisms of action.

Results

Initially, both drugs demonstrated concentration-dependent cytotoxicity in A549 cells. Also, their combination index (CI) indicated their synergistic effect at equi-IC50 concentration (CI = 0.00984). Moreover, Ator and/or Met-treated cells revealed disrupted patterns of SOD, CAT, GSH, MDA, and TAC, developed apoptosis, and larger fractions of the cell population were arrested in G0/G1 phase, particularly in cells dually-treated both Ator and Met. These observations were accompanied by downregulation in the expression of iNOS, HO-1, and the angiogenic marker VEGF, meanwhile, an altered expression of MAPK and AMPK was observed.

Conclusion

Conclusively, these data suggest that repurposing of Ator and Met demonstrates their individual and combined antiproliferative effect in non-small cell lung cancer and they may adopt a similar mechanism of action.

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阿托伐他汀和二甲双胍的再利用表明了它们在非小细胞肺癌中的单独和联合抗增殖作用。
背景:由于肺腺癌的治疗效果有限,迫切需要新的治疗方案来提高肺腺癌患者的治愈率和生存率:由于肺腺癌的治疗效果有限,因此迫切需要新的治疗方案来提高肺腺癌患者的治愈率和生存率:尽管他汀类药物(如阿托伐他汀(Atorvastatin,Ator))和二甲双胍(Met)分别作为降脂药和降糖药被广泛接受,但有很多人预测它们与传统化疗药联合使用会增强抗肿瘤效果:方法:在非小细胞肺癌(NSCLC)A549 细胞系中用 MTT 分析法检测了 Ator 和 Met 的单独和联合抗增殖潜力,并与吉西他滨(Gem)的相应作用进行了比较,同时对其作用机制进行了探讨:结果:最初,这两种药物在A549细胞中都表现出浓度依赖性细胞毒性。此外,它们的联合指数(CI)表明,在等效 IC50 浓度下,它们具有协同效应(CI = 0.00984)。此外,Ator 和/或 Met 处理过的细胞显示出 SOD、CAT、GSH、MDA 和 TAC 的紊乱模式,出现细胞凋亡,更多的细胞群停滞在 G0/G1 期,尤其是在同时使用 Ator 和 Met 的细胞中。这些观察结果伴随着 iNOS、HO-1 和血管生成标志物 VEGF 表达的下调,同时还观察到 MAPK 和 AMPK 表达的改变:总之,这些数据表明,Ator 和 Met 的再利用显示了它们在非小细胞肺癌中的单独和联合抗增殖作用,而且它们可能采用类似的作用机制。
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来源期刊
CiteScore
5.30
自引率
6.90%
发文量
111
审稿时长
6-12 weeks
期刊介绍: Fundamental & Clinical Pharmacology publishes reports describing important and novel developments in fundamental as well as clinical research relevant to drug therapy. Original articles, short communications and reviews are published on all aspects of experimental and clinical pharmacology including: Antimicrobial, Antiviral Agents Autonomic Pharmacology Cardiovascular Pharmacology Cellular Pharmacology Clinical Trials Endocrinopharmacology Gene Therapy Inflammation, Immunopharmacology Lipids, Atherosclerosis Liver and G-I Tract Pharmacology Metabolism, Pharmacokinetics Neuropharmacology Neuropsychopharmacology Oncopharmacology Pediatric Pharmacology Development Pharmacoeconomics Pharmacoepidemiology Pharmacogenetics, Pharmacogenomics Pharmacovigilance Pulmonary Pharmacology Receptors, Signal Transduction Renal Pharmacology Thrombosis and Hemostasis Toxicopharmacology Clinical research, including clinical studies and clinical trials, may cover disciplines such as pharmacokinetics, pharmacodynamics, pharmacovigilance, pharmacoepidemiology, pharmacogenomics and pharmacoeconomics. Basic research articles from fields such as physiology and molecular biology which contribute to an understanding of drug therapy are also welcomed.
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