Endoplasmic reticulum stress promotes autophagy and apoptosis and reverses chemoresistance in human ovarian cancer cells
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Jin-Long Hu1, Xin-Long Hu2, Ai-Ye Guo3, Chao-Jie Wang1, Yi-Yang Wen1 and Shun-Dong Cang1
1Department of Oncology, Henan Provincial People’s Hospital, Zhengzhou 450000, P. R. China
2Department of Medical Imaging Technology, Henan University of Chinese Medicine, Zhengzhou 450000, P. R. China
3Laboratory of Clinical Research, Henan Provincial People’s Hospital, Zhengzhou 450000, P. R. China
Jin-Long Hu, email: email@example.com
Shun-Dong Cang, email: firstname.lastname@example.org
Keywords: endoplasmic reticulum stress (ERS), ovarian cancer, PI3K/AKT/mTOR, autophagy, apoptosis
Received: July 04, 2016 Accepted: April 10, 2017 Published: May 07, 2017
Ovarian cancer presents the highest mortality rate among gynecological tumors. Here, we measured cell viability, proliferation, apoptosis, autophagy, and expression of endoplasmic reticulum stress (ERS)-related proteins, PI3K/AKT/mTOR pathway-related proteins, and apoptosis- and autophagy-related proteins in SKOV3 and SKOV3/CDDP cells treated with combinations of CDDP, tunicamycin, and BEZ235 (blank control, CDDP, CDDP + tunicamycin, CDDP + BEZ235, and CDDP + tunicamycin + BEZ235). Increasing concentrations of tunicamycin and CDDP activated ERS in SKOV3 cells, reduced cell viability and proliferation, increased apoptosis and autophagy, enhanced expression of ERS-related proteins, and inhibited expression of PI3K/AKT/mTOR pathway-related proteins. CDDP, tunicamycin, and BEZ235 acted synergistically to enhance these effects. We also detected lower expression of the ERS-related proteins caspase-3, LC3 II and Beclin 1 in ovarian cancer tissues than adjacent normal tissues. By contrast, expression of Bcl-2 and PI3K/AKT/mTOR pathway-related proteins was higher in ovarian cancer tissues than adjacent normal tissues. Lastly, expression of the ERS-related proteins Beclin 1, caspase-3 and LC3 II was higher in the sensitive group than the resistant group, while expression of Bcl-2, LC3 I, P62 and PI3K/AKT/mTOR pathway-related proteins was decreased. These results show that ERS promotes cell autophagy and apoptosis while reversing chemoresistance in ovarian cancer cells by inhibiting activation of the PI3K/AKT/mTOR signaling pathway.
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