首页|p32/OPA1 axis-mediated mitochondrial dynamics contributes to cisplatin resistance in non-small cell lung cancer

p32/OPA1 axis-mediated mitochondrial dynamics contributes to cisplatin resistance in non-small cell lung cancer

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Cisplatin resistance is a major obstacle in the treatment of non-small cell lung cancer(NSCLC).p32 and OPA1 are the key regulators of mitochondrial morphology and function.This study aims to investigate the role of the p32/OPA1 axis in cisplatin resistance in NSCLC and its underlying mechanism.The levels of p32 protein and mitochondrial fusion protein OPA1 are higher in cisplatin-resistant A549/DDP cells than in cisplatin-sensitive A549 cells,which facilitates mitochondrial fusion in A549/DDP cells.In addition,the expression of p32 and OPA1 protein is also upregulated in A549 cells during the development of cisplatin resistance.Moreover,p32 knockdown effectively downregulates the expression of OPA1,stimulates mitochondrial fission,decreases ATP generation and sensitizes A549/DDP cells to cisplatin-induced apoptosis.Furthermore,metformin significantly downregulates the expres-sions of p32 and OPA1 and induces mitochondrial fission and a decrease in ATP level in A549/DDP cells.The co-administration of metformin and cisplatin shows a significantly greater decrease in A549/DDP cell viability than cisplatin treatment alone.Moreover,D-erythro-Sphingosine,a potent p32 kinase activator,counteracts the met-formin-induced downregulation of OPA1 and mitochondrial fission in A549/DDP cells.Taken together,these find-ings indicate that p32/OPA1 axis-mediated mitochondrial dynamics contributes to the acquired cisplatin resistance in NSCLC and that metformin resensitizes NSCLC to cisplatin,suggesting that targeting p32 and mitochondrial dynamics is an effective strategy for the prevention of cisplatin resistance.

p32OPA1mitochondrial dynamicscisplatin resistancemetforminnon-small cell lung cancer

Chun-Xia Yu、Zhe-Qing Peng、Tao Wang、Xin-Hui Qu、Ping Yang、Shao-Rong Huang、Li-Ping Jiang、Fang-Fang Tou、Xiao-Jian Han

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Institute of Geriatrics,Jiangxi Provincial People's Hospital,The First Affiliated Hospital of Nanchang Medical College,Nanchang 330006,China

Department of Pharmacology,School of Pharmaceutical Science,Nanchang University,Nanchang 330006,China

The Second Department of Neurology,Jiangxi Provincial People's Hospital,the First Affiliated Hospital of Nanchang Medical College,Nanchang 330006,China

Department of Oncology,Jiangxi Provincial People's Hospital,The First Affiliated Hospital of Nanchang Medical College,Nanchang 330006,China

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国家自然科学基金Key Science and Technology Innovation Project of Jiangxi Provincial Health CommissionResearch Fund for Jiangxi Geriatric Clinical Medical Research CenterJiangxi Province Natural Science FoundationKey Projects from Department of Education of Jiangxi Province

820601772023ZD0012020BCG7400320224ACB206014GJJ218902

2024

10.3724/abbs.2023247

生物化学与生物物理学报(英文版)
中国科学院上海生物化学研究所

生物化学与生物物理学报(英文版)

CSTPCD
影响因子：0.772
ISSN：1672-9145
年,卷(期)：2024.56(1)
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