Attenuating glucose metabolism by Fbxw7 promotes Taxol sensitivity of colon cancer cells through downregulating NADPH oxidase 1 (Nox1)

作者：Huipeng Wang, Wenjie Chen, Jiamen Shen, Tao Ye, Hongwei Xie · 发表于：Annals of Translational Medicine · 年份：2021 · DOI：10.21037/atm-21-2076 · 被引用次数：13 · 研究领域：Neutrophil, Myeloperoxidase and Oxidative Mechanisms、Blood disorders and treatments、Cancer, Hypoxia, and Metabolism

Background: Colorectal cancer (CRC), one of the most common malignancies worldwide, is associated with poor survival and has a high mortality rate. Taxol is a chemotherapeutic agent that has been clinically applied as a first-line drug against diverse cancers. Yet, development of drug resistance has become the major challenge for anti-cancer treatments. F-box and WD40 domain protein 7 ( Fbxw7 ) is a known tumor suppressor which is frequently downregulated in cancers. However, the biological roles and mechanisms of Fbxw7 in Taxol resistance are still under investigation. Methods: We report that Fbxw7 is significantly inactivated in CRC tumors and cell lines compared with normal tissues and colon cells. Expressions of Fbxw7 and Nox1 were detected from human colon tumors and cells by qRT-PCR and Western blot. Glycolysis rate was assessed by glucose uptake and lactate product assay. Interactions between Fbxw7 and Nox1 were determined by co-immunoprecipitation (Co-IP). Chemosensitivity and resistance of colon cancer cells were determined by MTT assay and Annexin V-FITC assay. Results: Overexpression of Fbxw7 sensitized colon cancer cells to Taxol. Moreover, we observed a negative correlation between Fbxw7 and glucose metabolism. From the established Taxol-resistant (TR) cell line from HCT-116, Fbxw7 was found to be markedly downregulated in HCT-116 TR cells. We detected that NADPH oxidase 1 ( Nox1 ), a superoxide-generating NADPH oxidase, is negatively regulated by Fbxw7 . The Co-...