Endoplasmic reticulum stress regulates proliferation, migration and invasion of human ovarian cancer SKOV3 cells through PI3K/AKT/mTOR signaling pathway
Affiliations: [a] Department of Gynecological and Obstetric Ultrasound, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China | [b] Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, China
Correspondence:
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Corresponding author: Guang-Mei Zhang, Department of Gynecology and Obstetrics, The First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng Street, Nangang District, Harbin 150001, Heilongjiang, China. Tel.: +86 0451 85553453; E-mail: gmzrecho@163.com.
Abstract: OBJECTIVE: The study is to explore the role of tunicamycin-induced endoplasmic reticulum stress (ERS) in human ovarian cancer (OC) SKOV3 cells proliferation, migration and invasion by modulating the activity of PI3K/AKT/mTOR pathway. METHODS: The collected human OC SKOV3 cells were randomly separated into three groups: The control group, the Tun group (treated with tunicamycin to induce ERS) and the CHOP-si group (transfected with CHOP-siRNA before tunicamycin treatment). CCK-8 method was applied for testing cell proliferation, while flow cytometry was conducted to detect cell apoptosis. Scratch test and Transwell test were used to determine the level of cell migration and invasion, respectively. Western blotting was performed to determine the related proteins expressions in ERS and PI3K/AKT/mTOR pathway. RESULTS: The cell survival rate in the Tun group was enhanced than that in the CHOP-si group, both of which were declined with the passage of time. The cell apoptosis rate in the Tun group was increased compared to the CHOP-si group, both of which were significantly elevated. The horizontal migration distance and the number of invasive cells in the Tun and CHOP-si groups were inhibited; however, the horizontal migration distance and the number of invasive cells in the CHOP-si group were enhanced than that in the Tun group. In comparison with the control group, the expressions of CHOP and TRB3 were increased in the Tun group but decreased in the CHOP-si group. The PI3K, p-AKT and p-mTOR expressions were remarkably declined in the Tun group than those in the control group (P< 0.05). CONCLUSION: The study provides strong evidence that tunicamycin-induced ERS induces the apoptosis of human OC SKOV3 cells through inhibiting PI3K/AKT/mTOR signaling pathway.
