Capecitabine inhibits epithelial‑to‑mesenchymal transition and proliferation of colorectal cancer cells by mediating the RANK/RANKL pathway

Shao,Minghai; Jiang,Caiping; Yu,Changhui; Jia,Haijian; Wang,Yanli; Mao,Xinli

doi:10.3892/ol.2022.13216

Capecitabine inhibits epithelial‑to‑mesenchymal transition and proliferation of colorectal cancer cells by mediating the RANK/RANKL pathway

Authors:
- Minghai Shao
- Caiping Jiang
- Changhui Yu
- Haijian Jia
- Yanli Wang
- Xinli Mao
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Affiliations: Department of Radiation Oncology, Key Laboratory of Minimally Invasive Techniques and Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang 317000, P.R. China, Department of Gastroenterology, Key Laboratory of Minimally Invasive Techniques and Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang 317000, P.R. China
Published online on: January 27, 2022 https://doi.org/10.3892/ol.2022.13216
Article Number: 96
Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is the third most prevalent malignancy globally. Capecitabine is an important form of chemotherapy for colorectal cancer. The present study aims to investigate the underlying mechanism of action of the drug in CRC cells. In the present study, 50 pairs of CRC and adjacent normal tissues were collected, and CRC cell lines (SW480, SW620, HT29, LOVO and HCT116) and NCM460 colonic epithelial cells were also purchased and used. Western blotting was used to measure the expression levels of proteins involved in the receptor activator of nuclear factor‑κB (RANK)/receptor activator of nuclear factor‑κB ligand (RANKL) pathway and epithelial‑to‑mesenchymal transition (EMT), including RANK, RANKL, osteoprotegerin (OPG), E‑cadherin, vimentin and N‑cadherin. Proliferation and migration were measured using MTT, Cell Counting Kit‑8, EdU, Transwell and wound healing assays, respectively. In the present study, it was found that the RANK/RANKL pathway was activated in cancer tissues and cells. Additionally, it was observed that capecitabine treatment reduced the protein expression of RANK, RANKL and OPG in HT29 cells, suggesting that capecitabine has a repressive effect on the RANK/RANKL pathway. Furthermore, functional experiments revealed that the proliferative ability and the EMT process observed in HT29 cells were inhibited after they were treated with capecitabine or transfected with si‑RANK. Rescue assays were then performed, which revealed that the promotion of RANK via transfection of cells with 50 nM pcDNA3.1‑RANK reversed the inhibitory effects of capecitabine on HT29 cell proliferation and EMT. These findings suggest that the regulatory role of capecitabine is at least partially mediated through the RANK/RANKL pathway in colorectal cancer. The present study demonstrated that capecitabine‑induced repression of CRC is exerted by inhibiting the RANK/RANKL pathway, where this new mechanism potentially provides a novel therapeutic target.

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