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apolipoprotein e2 inhibits mitochondrial apoptosis in pancreatic cancer cells through eRK1/2/CReB/BCL-2 signaling

Hepatobiliary & Pancreatic Diseases International 2023年第2期22卷 179-189页

作者： Hui Wang Hui-Chao Zhou Run-Ling Ren Shao-Xia Du Zhong-Kui Guo Xiao-Hong Shen Tianjin Institute of Medical&Pharmaceutical Sciences Tianjin 300020China School of Medicine Nankai UniversityTianjin 300071China

Background: apolipoprotein e2(Apoe2) is a pleiotropic protein that influences several aspects of cancer metabolism and development. evading apoptosis is a vital factor for facilitating cancer cell growth. However, the role and mechanism of Apoe2 in regulating cell apoptosis of pancreatic cancer remain unclear. Methods: In this study, we firstly detected the m RNA and protein expressions of Apoe2 in PANC-1 and Capan-2 cells by real-time polymerase chain reaction and Western blotting. We then performed TUNeL and flow cytometric analyses to explore the role of recombinant human Apoe2, p CMV6-Apoe2 and si Apoe2 in the apoptosis of PANC-1 and Capan-2 cells. Furthermore, we investigated the molecular mechanism through which Apoe2 affected apoptosis in PANC-1 cells using immunofluorescence, immunoprecipitation, Western blotting and co-immunoprecipitation analysis. Results: Apoe2 phosphorylated eRK1/2 and inhibited pancreatic cancer cell apoptosis. In addition, our data showed that Apoe2/eRK1/2 altered the expression and mitochondrial localization of BCL-2 via activating CReB. Apoe2/eRK1/2/CReB also increased the total BCL-2/BAX ratio, inhibited the opening of the mitochondrial permeability transition pore and the depolarization of mitochondrial transmembrane potential, blocked the leakage of cytochrome-c and the formation of the apoptosome, and consequently, suppressed mitochondrial apoptosis. Conclusions: Apoe2 regulates the mitochondrial localization and expression of BCL-2 through the activation of the eRK1/2/CReB signaling cascade to evade the mitochondrial apoptosis of pancreatic cancer cells. Apoe2 may be a distinct prognostic marker and a potential therapeutic target for pancreatic cancer.

关键词： apolipoprotein e2 eRK1/2 Mitochondrial apoptosis Pancreatic cancer

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