Jafarzadeh Emad, Sarajar Behnam Omidi, Lalani Armineh Rezaghol, Rastegar-Pouyani Nima, Aliebrahimi Shima, Montazeri Vahideh, Ghahremani Mohammad H, Ostad Seyed Nasser
Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Curr Top Med Chem. 2025 Feb 11. doi: 10.2174/0115680266317788241121100259.
The persistent drug resistance observed in lung cancer necessitates innovative strategies to improve therapeutic outcomes. This review investigates the potential of combining metformin (Met) and cisplatin (Cis) to overcome drug resistance and enhance treatment efficacy. Cis's limitations, including drug resistance and adverse effects, coupled with Met's established safety profile, form the backdrop for this exploration.
Systematic literature searches across major databases identified relevant studies exploring the synergistic effects of Met and Cis in the context of drug-resistant lung cancer. Data extraction encompassed diverse facets, including treatment protocols, cellular responses, and mechanistic insights. The synthesis of these findings sheds light on the potential of this combination therapy to combat drug resistance.
Numerous in vitro and in vivo studies have demonstrated the ability of the Met + Cis combination to sensitize drug-resistant lung cancer cells. The co-treatment consistently showed enhanced inhibition of cell proliferation, elevated apoptosis rates, and attenuated migration and invasion capabilities compared to monotherapies. Mechanistically, Met's modulatory effect on key pathways, such as AMPK-mTOR and ROS-mediated signaling, appears to underlie its ability to counter drug resistance.
The Met + Cis combination holds promise as an innovative strategy to counter drug resistance in lung cancer. By harnessing the synergistic effects of these agents, combination therapy offers a novel approach to enhance treatment efficacy and mitigate the challenges posed by drug-resistant lung cancer. Although further clinical validation is required, the Met + Cis synergy represents a promising avenue in the pursuit of improved lung cancer therapy outcomes.
肺癌中观察到的持续耐药性需要创新策略来改善治疗效果。本综述研究了联合使用二甲双胍（Met）和顺铂（Cis）以克服耐药性并提高治疗效果的潜力。顺铂的局限性，包括耐药性和不良反应，再加上二甲双胍已确立的安全性，构成了本次探索的背景。
在各大数据库中进行系统的文献检索，以确定探索二甲双胍和顺铂在耐药性肺癌背景下协同作用的相关研究。数据提取涵盖多个方面，包括治疗方案、细胞反应和机制见解。这些研究结果的综合揭示了这种联合疗法对抗耐药性的潜力。
大量的体外和体内研究表明，二甲双胍+顺铂联合用药能够使耐药性肺癌细胞敏感化。与单一疗法相比，联合治疗始终显示出对细胞增殖的抑制增强、凋亡率升高以及迁移和侵袭能力减弱。从机制上讲，二甲双胍对关键通路（如AMPK-mTOR和ROS介导的信号传导）的调节作用似乎是其对抗耐药性的能力基础。
二甲双胍+顺铂联合用药有望成为对抗肺癌耐药性的创新策略。通过利用这些药物的协同作用，联合疗法提供了一种新方法来提高治疗效果并减轻耐药性肺癌带来的挑战。尽管需要进一步的临床验证，但二甲双胍+顺铂的协同作用代表了在追求改善肺癌治疗效果方面的一条有前途的途径。
