β-Elemene Reverses the Resistance of p53-Deficient Colorectal Cancer Cells to 5-Fluorouracil by Inducing Pro-death Autophagy and Cyclin D3-Dependent Cycle Arrest

作者：Ruonan Zhang, Ting Pan, Xiang Yu, Mingming Zhang, Jiao Feng, Shuiping Liu, Ting Duan, Peng Chen, Bingtao Zhai, Xiaying Chen, Wengang Wang, Bi Chen, Xuemeng Han, Liuxi Chen, Lili Yan, Ting Jin, Ying Liu, Guohua Li, Xingxing Huang, Wenzheng Zhang, Yitian Sun, Qiujie Li, Qin Zhang, Lvjia Zhuo, Tian Xie, Qibiao Wu, Xinbing Sui · 发表于：Frontiers in Bioengineering and Biotechnology · 年份：2020 · DOI：10.3389/fbioe.2020.00378 · 被引用次数：54 · 研究领域：Autophagy in Disease and Therapy、Cancer-related Molecular Pathways、Metabolism, Diabetes, and Cancer

Objective: Colorectal cancer is the third most common cancer worldwide and the second most common cancer cause of death worldwide. 5-fluorouracil remains a widely used chemotherapeutic drug in the treatment of advanced colorectal cancer, but chemotherapy drugs are prone to drug resistance, p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to 5-fluorouracil. β-elemene has been proved to have the potential of reverse chemotherapy drug resistance, but the mechanism is unknown. This study aimed to investigate the effect of β-elemene to 5-fluorouracil in drug-resistant p53-deficient colorectal cancer cells HCT116p53-/-, and determine the possible molecular mechanism of β-elemene to reverse 5-fluorouracil resistance. Methods: The effect of β-elemene on HCT116p53-/- cell activity was detected by Cell counting Kit-8. Cell proliferation was detected by monoclonal plate. The apoptosis was detected by flow cytometry and western blot. The autophagy was detected by western blot, immunofluorescence and transmission electron microscope. Determine the role of Cyclin-related protein Cyclin D3 in β-elemene reversing the resistance of HCT116p53-/- to 5-fluorouracil was detected by overexpression of Cyclin D3. The effect of β-elemene on the tumorigenic ability of p53-deficient colorectal cancer cells was detected establishing HCT116p53-/- all line xenograft model. Results: For p53 wildtype colorectal cancer cells, β-elemene could augment the sensitivit...