Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial‑mesenchymal transition

Zheng,Jianyun; Yu,Jianxin; Yang,Min; Tang,Li

doi:10.3892/etm.2019.7754

Gefitinib suppresses cervical cancer progression by inhibiting cell cycle progression and epithelial‑mesenchymal transition

Authors:
- Jianyun Zheng
- Jianxin Yu
- Min Yang
- Li Tang
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Affiliations: Department of Pathology, The First Affiliated Hospital of Xi'an Medical University, School of General Medicine, Xi'an Medical University, Xi'an, Shaanxi 710077, P.R. China, Department of Laboratory, Central Hospital of Shanxian County, Heze, Shandong 274399, P.R. China, Department of Gynaecology and Obstetrics, Puyang Oil Field General Hospital, Puyang, Henan 457001, P.R. China
Published online on: July 9, 2019 https://doi.org/10.3892/etm.2019.7754
Pages: 1823-1830

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Abstract

Cervical cancer (CC) is the second most common malignant cancer among women. Gefitinib was one of the first‑generation epidermal growth factor receptor‑tyrosine kinase inhibitors in clinical trials. However, the underlying mechanism of gefitinib in regulating CC progression remains unknown. In the current study, two CC cell lines, HeLa and Siha, were used to investigate the effects of gefitinib. Cell counting kit‑8 assays demonstrated that treatment with gefitinib exerted strong cytotoxicity in HeLa and Siha cells. Flow cytometry was used to examine cell cycle progression and apoptosis. Treatment with gefitinib enhanced the number of cells in the G0/G1 phase and increased apoptosis in HeLa and Siha cells. Furthermore, treatment with gefitinib decreased the protein expression level of Bcl‑2 and increased the protein expression level of Bax. Taken together, these results suggest that gefitinib may suppress CC cell proliferation and induce cell cycle arrest and apoptosis. The current study also demonstrated that treatment with gefitinib suppressed epithelial‑mesenchymal transition (EMT) as the expression level of the epithelial marker, E‑cadherin was increased, while the expression level of the mesenchymal marker, vimentin was decreased. The current study demonstrated that treatment with gefitinib decreased the protein expression levels of phosphorylated‑GSK3β and β‑catenin, which suggests that gefitinib may be a potential novel therapeutic strategy in CC by suppressing the Wnt/β‑catenin signaling pathway and EMT to inhibit tumor metastasis in CC cells. In conclusion, gefitinib may suppress the EMT process during cell invasion and induce cell apoptosis and cell cycle arrest via inhibition of the Wnt/β‑catenin signaling pathway.

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