Simvastatin is involved in radioresistance of esophageal cancer cells by regulating the PI3K/AKT pathway-mediated epithelial-mesenchymal transition
- Author:
Ying-Ying JIN
1
Author Information
- Publication Type:Journal Article
- Keywords: EMT; Esophageal cancer; PI3K/AKT; Radiosensitivity; Simvastatin
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2019;40(1):32-37
- CountryChina
- Language:Chinese
- Abstract: Objective: To explore the role and mechanism of simvastatin in radioresistance and epithelial-mesenchymal transition (EMT) of esophageal cancer. Methods: Esophageal cancer cells were preconditioned with simvastatin (5 μmol/L) for 8 h, prior to exposure to x-ray irradiation. Clonogenic cell survival assay was performed to detect cell survival fraction. Cell proliferation was evaluated by MTT assay. Cell apoptosis was determined by flowcytometry. The activity of caspase-3 was detected by the common commercial kit. Additionally, Western blot assay was performed to analyze the activation of the PI3K/AKT pathway. Results: Pretreatment with simvastatin dramatically decreased the survival fraction (P<0.05) and proliferation (P<0.05) of the radiated cells, but aggravated cell apoptosis rate and caspase-3 activity (P<0.05). Furthermore, simvastatin stimulation significantly increased the expression of epithelial marker E-cadherin in 6 Gy-treated cells, but down-regulated the expression of mesenchymal marker N-cadherin and Vimentin (P<0.05). Mechanism analysis corroborated the activation of the PI3K/AKT pathway in cells after irradiation by elevating the expression of p-AKT, which was abrogated by simvastatin pre-treatment. More importantly, administration with IGF-1, an activator of PI3K/AKTpathway, attenuated the inhibitory effect of simvastatin on radioresistance and radiation-evoked EMT (P<0.05). Conclusion: Simvastatin inhibits radiation-induced EMT of esophageal cancer cells by blocking the PI3K/AKT pathway, and ultimately elevates the radiosensitivity, indicating a promising therapeutic avenue for treatment of esophageal cancer radioresistance.
