RIPK1 contributes to cisplatin-induced apoptosis of esophageal squamous cell carcinoma cells via activation of JNK pathway.

Autor: Zhang Y; Department of Thoracic Surgery, Dingyuan County General Hospital of Chuzhou City in Anhui, Anhui 233200, China., Du J; Department of Oncology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230036, China., Duan X; Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China. Electronic address: xiaofan_duan@126.com., Peng W; Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China. Electronic address: pengwei8324@126.com., Lv L; Anhui Provincial Cancer Hospital, West Branch of the First Afliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230031, Anhui, China. Electronic address: lvlei@ustc.edu.cn., Chen Z; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China. Department of Oncology, Shanghai Medical College, Fudan University, 130 Dong An Road, Shanghai 200032, China. Electronic address: chanhj75@aliyun.com., Zhang Y; Department of VIP Clinic, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200123, China. Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China. Electronic address: zymhefei@163.com.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2021 Mar 15; Vol. 269, pp. 119064. Date of Electronic Publication: 2021 Jan 15.
DOI: 10.1016/j.lfs.2021.119064
Abstrakt: Aims: Previous studies have uncovered the function of receptor-interacting protein kinase 1 (RIPK1) to mediate both cell survival and death. Moreover, RIPK1 modulates apoptosis and necroptosis depending on its activity, phosphorylation or ubiquitylation status. Many studies have explained the role or mechanism of RIPK1 in necroptosis. However, the role of RIPK1 has not been elucidated fully in human esophageal squamous cell carcinoma (ESCC) cells.
Materials and Methods: The protein and mRNA expression levels of RIPK1 in a panel of ESCC cell lines by Western blot and real-time quantitative reverse transcription PCR (qRT-PCR) were analyzed. MTS assay was used to examine cellular proliferation, flow cytometric analysis to detect apoptosis, mitochondrial membrane potential and reactive oxygen species production. ESCC cells with either inhibitor or overexpressed RIPK1were analyzed to determine cell proliferation, colony formation and apoptosis. Flow cytometry and western blotting assays were used to explore the underlying mechanism.
Key Findings: In our study, RIPK1 expression was found to contribute significantly to cisplatin-induced apoptosis in the human ESCC cells. The reduced RIPK1 expression promoted cells proliferation and overexpressed RIPK1 facilitated cell apoptosis. Mechanistic investigations have revealed that the inhibition of proliferation for RIPK1 in ESCC cells was regulated via activation of c-Jun NH2-terminal kinase signaling. Additionally, damages were observed in the mitochondrial membrane, depletion of ATP and increased generation in reactive oxygen species.
Significance: Our findings verified the evidence that RIPK1 can promote cell death in ESCC cells, with potential implications for activating c-Jun NH2-terminal kinase pathway as a novel approach to the disease.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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