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題名:Successive treatment with naltrexone induces epithelial–mesenchymal transition and facilitates the malignant biological behaviors of bladder cancer cells.
作者:Xiaoqiang Wang, Ruirui Zhang, Tong Wu, Yumiao Shi, Xiao Zhou, Dan Tang, Weifeng Yu, Edmund Cheung So, Xiaodan Wu, Zhiying Pan, Jie Tian
期刊名稱:Biochimica et Biophysica Sinica
發表頁數:238-248
發表年份:2021
發表月份:2
摘要:Naltrexone is widely used for alleviating opioid-related side effects in cancer patients. However, the effects of naltrexone on cancer progression are controversial in the literature. The present study was carried out to investigate the effects of successive treatment with clinically relevant doses of naltrexone on the malignant biological behaviors of bladder cancer cells. The human bladder cancer T24 cells and mouse bladder cancer MB49 cells were treated with naltrexone. Cell proliferation, migration, and invasion abilities were analyzed. Morphological changes of the cells were confirmed by F-actin immunofluorescence staining. Epithelial-mesenchymal transition (EMT)-related markers and transcriptional factors, as well as activation of the phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway, were analyzed. Results showed that, compared with the control group, successive treatment with naltrexone significantly promoted the proliferation and decreased the apoptosis of bladder cancer cells, together with increase in cell migration and invasion ability. Continuous treatment with naltrexone also significantly reduced the expression of epithelial markers (E-cadherin and cytokeratin 19), increased the expression of mesenchymal markers (N-cadherin and vimentin) and EMT-inducing transcription factors (Snail and Slug), and further shifted the morphological phenotype of bladder cancer cells to a mesenchymal phenotype. The PI3K/AKT signaling pathway was activated by successive treatment with naltrexone. Notably, incubation with the specific PI3K inhibitor LY294002 together with naltrexone reversed the naltrexone-induced EMT progression. In conclusion, successive treatment with naltrexone may be favorable for the progression of bladder tumors by activating the PI3K/AKT signaling pathway and inducing EMT. Long-term exposure to naltrexone should be used cautiously in patients with bladder cancer.
關鍵字:
英文關鍵字:bladder cancer; epithelial–mesenchymal transition; naltrexone
DOI:10.1093/abbs/gmaa169
Vol:53
NO:2
ISSN:ISSN 1745-7270