Synergistic induction of autophagy in gastric cancer by targeting CDK4/6 and MEK through AMPK/mTOR pathway

Hong Zhou; Guiling Li; Liuyue Kan; Mingyu Yang; Yu Liu; Xiaye Miu; Lei Shi; Zhanjun Yang; Xucai Zheng; Hui Chen; Chuanli Ren

Heliyon (May 2024)

Synergistic induction of autophagy in gastric cancer by targeting CDK4/6 and MEK through AMPK/mTOR pathway

Hong Zhou,
Guiling Li,
Liuyue Kan,
Mingyu Yang,
Yu Liu,
Xiaye Miu,
Lei Shi,
Zhanjun Yang,
Xucai Zheng,
Hui Chen,
Chuanli Ren

Affiliations

Hong Zhou: Department of Laboratory Medicine, Clinical College of Yangzhou University and Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, China
Guiling Li: Department of Laboratory Medicine, Clinical College of Yangzhou University and Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, China
Liuyue Kan: Department of Laboratory Medicine, Clinical College of Yangzhou University and Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, China
Mingyu Yang: Department of Laboratory Medicine, Clinical College of Yangzhou University and Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, China
Yu Liu: Department of Laboratory Medicine, Clinical College of Yangzhou University and Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, China
Xiaye Miu: Department of Laboratory Medicine, Clinical College of Yangzhou University and Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, China
Lei Shi: Department of Gastrointestinal Surgery, Clinical College of Yangzhou University, Yangzhou, Jiangsu, 225001, China
Zhanjun Yang: Department of Chemistry, Yangzhou University, Yangzhou, Jiangsu, 225002, China; Corresponding author.
Xucai Zheng: Department of Breast and Thyroid Surgery, the First Affiliated Hospital of University of Science and Technology of China, Hefei, Anhui, 230031, China; Corresponding author.
Hui Chen: Department of Geriatrics, Clinical College of Yangzhou University, Yangzhou, Jiangsu, 225001, China; Corresponding author.
Chuanli Ren: Department of Laboratory Medicine, Clinical College of Yangzhou University and Northern Jiangsu People's Hospital, Yangzhou, Jiangsu, 225001, China; Department of Laboratory Medicine, Clinical College of Xuzhou Medica University, Yangzhou, Jiangsu, 225001, China; Corresponding author. Department of Laboratory Medicine, Clinical College of Yangzhou University, Clinical College of Xuzhou Medica University and Northern Jiangsu People's Hospital, Jiangsu,225001, China.

Journal volume & issue: Vol. 10, no. 9
p. e30475

Abstract

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KRAS is a commonly mutated oncogene in human gastric cancer and is often associated with drug resistance and poor prognosis. Co-clinical trial of combined MEK-CDK4/6 inhibition in KRAS mutated cancers demonstrated therapeutic efficacy in patient-derived xenografts and safety in patients. Here, present research focuses on targeting CDK4/6 and MEK synergistically block the proliferation of KRAS-mutated gastric cancer cells in vitro and in vivo and induced autophagy through the AMPK/mTOR pathway. Furthermore, autophagy inhibitor combined with targeting CDK4/6 and MEK therapy had significant antitumor effects on KRAS mutant gastric cancer cells. Clinical trials are needed to determine the mechanism behind this finding and its clinical utility. In conclusion, our results demonstrate autophagy inhibitor combined targeting MEK and CDK4/6 that concurrently block multiple metabolic processes may be an effective therapeutic approach for gastric cancer.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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