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S100A9 regulates cisplatin chemosensitivity of squamous cervical cancer cells and related mechanism

Authors Zhao C, Lu E, Hu X, Cheng H, Zhang JA, Zhu X

Received 15 March 2018

Accepted for publication 25 June 2018

Published 20 September 2018 Volume 2018:10 Pages 3753—3764

DOI https://doi.org/10.2147/CMAR.S168276

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Professor Lu-Zhe Sun


Chuchu Zhao,* Ermei Lu,* Xiaoli Hu, Huihui Cheng, Jian-An Zhang, Xueqiong Zhu

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China

*These authors contributed equally to this work

Objective: Our previous research has shown that the expression of S100 calcium-binding protein A9 (S100A9) in tumor cells was associated with neoadjuvant chemotherapy sensitivity in cervical squamous cell carcinoma. In the present study, we altered the expression of S100A9 through infecting lentivirus, investigated its effect on the chemosensitivity to cisplatin of cervical cancer cells and then made a primary exploration of the involved mechanism.
Materials and methods: Lentivirus was employed to upregulate and downregulate S100A9 expression in SiHa cells. The protein expression level of apoptotic-related proteins Bcl-2 and Bax, drug resistance-related proteins multiple drug resistance protein 1 (MRP1), P glycoprotein (P-gp), glutathione-S-transferase-π (GST-π), lung resistance-related protein (LRP), and FOXO1 signaling pathway related proteins was detected by Western blot. The CCK-8 assay was used to examine chemosensitivity to cisplatin, and the proportion of apoptosis cells was analyzed by the flow cytometry.
Results: S100A9 overexpression could obviously increase the IC50 value of SiHa cells to cisplatin and decrease the apoptosis rate induced by cisplatin. Downregulation of S100A9 led to the opposite results. In S100A9 overexpression SiHa cells, the expression level of Bcl-2, LRP, GST-π, p-AKT, p-ERK, p-FOXO1, and Nanog was significantly increased, while FOXO1 expression was decreased. The opposite results were observed in S100A9 knockdown SiHa cells.
Conclusion: Downregulation of S100A9 could significantly increase apoptosis rate, resulting in enhancing sensitivity of SiHa cells to cisplatin, which may be related to Bcl-2, GST-π, and LRP protein and by altering the AKT/ERK-FOXO1-Nanog signaling pathway.

Keywords: S100A9, cervical cancer, Bcl-2, GST-π, LRP, FOXO1, cisplatin, chemosensitivity

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