Ferroptosis as a Potential Cell Death Mechanism against Cisplatin-Resistant Lung Cancer Cell Line

Golbashirzadeh, Morteza and Heidari, Hamid Reza and Talebi, Mehdi and Yari Khosroushahi, Ahmad (2021) Ferroptosis as a Potential Cell Death Mechanism against Cisplatin-Resistant Lung Cancer Cell Line. Advanced Pharmaceutical Bulletin. ISSN 2228-5881

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Abstract

Purpose: Drug resistance is a challenging issue in cancer chemotherapy. Cell death induction is one of the main strategies to overcome chemotherapy resistance. Notably, ferroptosis has been considered a critical cell death mechanism in recent years. Accordingly, in this study, the different cell death strategies focused on ferroptosis have been utilized to overcome cisplatin resistance in an in vitro lung cancer model.

Methods: The physiological functions of Akt1 and GPX4, as critical targets for ferroptosis and apoptosis induction, were suppressed by siRNA or antagonistic agents in resistant A549 cells. Afterward, the interventions’ impacts on cell viability and reactive oxygen species (ROS) amount were analyzed by flow cytometry. Moreover, the alteration in the relevant gene and protein expression levels were quantified using Real-time PCR and western blot methods.

Results: The result showed that the treatment with Akt1 siRNA reversed the cisplatin resistance in the A549 cell line through the induction of apoptosis. Likewise, the combination treatment of the GPX4 siRNA or FIN56 as ferroptosis inducers alongside cisplatin elevated ROS’s cellular level, reduced the cellular antioxidant genes level and increased the cisplatin cytotoxic effect.

Conclusion: In conclusion, our study indicated that ferroptosis induction can be considered a promising cell death strategy in cisplatin-resistant cancer cells.

Item Type: Article
Subjects: STM Digital > Medical Science
Depositing User: Unnamed user with email support@stmdigital.org
Date Deposited: 17 Mar 2023 08:55
Last Modified: 30 May 2024 13:35
URI: http://research.asianarticleeprint.com/id/eprint/380

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