Triptolide inhibits epithelial-mesenchymal transition phenotype through the p70S6k/GSK3/beta-catenin signaling pathway in taxol-resistant human lung adenocarcinoma

Tian, Yu and Li, Peiwei and Xiao, Zhaohua and Zhou, Jie and Xue, Xia and Jiang, Ning and Peng, Chuanliang and Wu, Licun and Tian, Hui and Popper, Helmut and Poh, Mau-Ern and Marcucci, Fabrizio and Zhang, Chengke and Zhao, Xiaogang (2021) Triptolide inhibits epithelial-mesenchymal transition phenotype through the p70S6k/GSK3/beta-catenin signaling pathway in taxol-resistant human lung adenocarcinoma. Translational Lung Cancer Research, 10 (2). 1007+. ISSN 2218-6751, DOI

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Chemotherapy is one of the primary treatments for both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), however, chemoresistance develops over time and is a bottleneck to effective chemotherapy worldwide. Therefore, the development of new potent therapeutic agents to overcome chemoresistance is of utmost importance. Triptolide is a natural component extracted from Tripterygium Wilfordii, a Chinese plant; our study aimed to evaluate its anti-tumor effects in taxol-resistant human lung adenocarcinoma and investigate its molecular mechanisms of chemoresistance. Methods: Triptolide's inhibition of cell viability was detected by sulforhodamine B (SRB) assay. Cell cycle was measured by flow cytometry and cell apoptosis was assessed by flow cytometry and western blot. Expression of 0-catenin was analyzed by western blot and immunofluorescence (IF). The anti-tumor effects of triptolide were determined using a subcutaneous in-vivo model. Cell proliferation and apoptosis were evaluated by immunohistochemistry (IHC) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. The expression level of p-p70S6K and p-GSK-3 alpha/0 was evaluated by western blot and IHC. Results: Triptolide inhibited cell proliferation, induced S-phase cell cycle arrest and apoptosis in taxolresistant A549 (A549/TaxR) cells. Moreover, intraperitoneal injection of triptolide resulted in a significant delay of tumor growth without obvious systemic toxicity in mice. Additionally, triptolide reversed epithelialmesenchymal transition (EMT) through repression of the p70S6K/GSK3/0-catenin signaling pathway. Conclusions: Our study provides evidence that triptolide can reverse EMT in taxol-resistant lung adenocarcinoma cells and impairs tumor growth by inhibiting the p70S6K/GSK3/0-catenin pathway, indicating that triptolide has potential to be used as a new therapeutic agent for taxol-resistant lung adenocarcinoma.

Item Type: Article
Funders: National Natural Science Foundation of China (NSFC)[81874396], Major Program of Shandong Province Natural Science Foundation[ZR2018ZC0232], Jinan Clinical Medicine Research Program for Thoracic Cancer[201912007], Special Construction Project Fund for Taishan Mountain Scholars of Shandong Province
Uncontrolled Keywords: Lung adenocarcinoma;Triptolide;Chemoresistance;Epithelial-mesenchymal transition (EMT);Wnt
Subjects: R Medicine
R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 15 Sep 2022 03:11
Last Modified: 15 Sep 2022 03:11

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