Small interfering RNA targeting N‑cadherin regulates cell proliferation and migration in enzalutamide‑resistant prostate cancer

Lu,Cheng-Hsin; Wu,Chun-Hsien; Hsieh,Pei-Fang; Wu,Chen-Yu; Kuo,Wade Wei‑Ting; Ou,Chien-Hui; Lin,Victor Chia Hsiang

doi:10.3892/ol.2022.13210

Small interfering RNA targeting N‑cadherin regulates cell proliferation and migration in enzalutamide‑resistant prostate cancer

Authors:
- Cheng-Hsin Lu
- Chun-Hsien Wu
- Pei-Fang Hsieh
- Chen-Yu Wu
- Wade Wei‑Ting Kuo
- Chien-Hui Ou
- Victor Chia Hsiang Lin
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Affiliations: Division of Urology, Penghu Hospital, Penghu 880001, Taiwan, R.O.C., Division of Urology, Department of Surgery, E‑Da Hospital, Kaohsiung 824005, Taiwan, R.O.C., Department of Urology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704302, Taiwan, R.O.C.
Published online on: January 21, 2022 https://doi.org/10.3892/ol.2022.13210
Article Number: 90
Copyright: © Lu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Enzalutamide is one of the options for treating patients with castration‑resistant or metastatic prostate cancer. However, a substantial proportion of patients become resistant to enzalutamide after a period of treatment. Cells in these tumors typically exhibit increased proliferative and migratory capabilities, in which N‑cadherin (CDH2) appear to serve an important role. In the present study, by up‑ and downregulating the expression of CDH2, the possible effects of CDH2 on the prostate cancer cell line LNCaP were investigated. Male sex hormone‑sensitive LNCaP cells treated with 10 µM enzalutamide were named LNCaP enzalutamide‑resistant (EnzaR) cells. Reverse transcription‑PCR, western blotting and immunofluorescence staining were used to measure CDH2, E‑cadherin, α‑SMA, Snail and Slug expression. Transfection with the pCMV‑CDH2 plasmid was performed for CDH2 upregulation, whilst transfection with small interfering RNA (siRNA)‑CDH2 was performed for CDH2 downregulation. MTT and Cell Counting Kit‑4 assays were used to evaluate the proportion of viable cancer cells. Subsequently, gap closure assay was performed to evaluate the migratory capability of both LNCaP and LNCaP EnzaR cell lines. CDH2 expression was found to be increased in LNCaP EnzaR cells compared with that in LNCaP cells. CDH2 overexpression increased cell viability and migration in both LNCaP and LNCaP EnzaR cell lines. By contrast, the opposite trend was observed after CDH2 expression was knocked down. CDH2 expression also showed a high association with that of four epithelial‑mesenchymal transition markers, which was confirmed by western blotting. Based on these results, it was concluded that knocking down CDH2 expression using siRNA transfection mediated significant influence on LNCaP EnzaR cell physiology, which may be a potential therapeutic option for prostate cancer treatment.

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