Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA‑374a/forkhead box O1 signaling axis

Sun,Yang; Peng,Yong‑Bao; Ye,Ling‑Ling; Ma,Long‑Xian; Zou,Mei‑Yan; Cheng,Zhong‑Gui

doi:10.3892/mmr.2020.10943

Propofol inhibits proliferation and cisplatin resistance in ovarian cancer cells through regulating the microRNA‑374a/forkhead box O1 signaling axis

Authors:
- Yang Sun
- Yong‑Bao Peng
- Ling‑Ling Ye
- Long‑Xian Ma
- Mei‑Yan Zou
- Zhong‑Gui Cheng
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Affiliations: Department of Anesthesiology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330003, P.R. China, Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Obstetrics and Gynecology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330003, P.R. China
Published online on: January 16, 2020 https://doi.org/10.3892/mmr.2020.10943
Pages: 1471-1480
Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ovarian cancer is a prominent disease that demonstrates high incidence rates in women and often presents multidrug resistance. Propofol has been demonstrated to suppress the malignancy of various types of human cancer; however, the underlying molecular mechanisms of propofol in ovarian cancer remain largely unknown. The present study aimed to investigate whether and how propofol inhibits proliferation and cisplatin (DDP) resistance in ovarian cancer cells. Ovarian cancer cell viability was assessed by the Cell Counting kit‑8 assay; apoptosis and cell cycle progression were determined by flow cytometry; the relative expression levels of microRNA (miR)‑374a and forkhead box O1 (FOXO1) were analyzed using reverse transcription‑quantitative PCR; the binding ability of miR‑374a to FOXO1 was assessed by the dual‑luciferase reporter assay; cellular sensitivity to DDP was detected using the MTT assay; and finally, the protein expression levels of FOXO1, p27, and Bcl‑2‑like‑protein 11 (Bim) were analyzed by western blotting. Propofol reduced viability, promoted apoptosis and decreased miR‑374a expression levels in A2780 cells. In addition, the viability of A2780/DDP cells in the propofol + DDP treatment group was significantly inhibited, and the apoptotic rate was increased. In addition, miR‑374a overexpression increased cell viability and the proportion of cells in the S phase, and decreased the proportion of cells in the G0/G1 phase. Conversely, genetic knockdown of miR‑374a exerted the opposite effects on cell viability and cell cycle progression. Moreover, miR‑374a was demonstrated to bind to FOXO1. Propofol promoted the expression of FOXO1, p27 and Bim, induced cell cycle arrest and decreased ovarian cancer cell viability. In addition, treatment with propofol and DDP regulated FOXO1 and increased apoptosis of ovarian cancer cells. In conclusion, propofol downregulated miR‑374a and modulated the FOXO1 pathway to reduce proliferation and DDP resistance in ovarian cancer cells.

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