Mobile website
Archive > Volume 28 Issue 2 > 2021,28(2):115-120. DOI:10.3872/j.issn.1007-385x.2021.02.003 Prev Next
Basic Research
Micheliolide enhances the sensitivity of colorectal cancer cells to oxaliplatin by promoting autophagy
- Article
- Figures
- Metrics
- Preview PDF
- Reference
- Related
- Cited by
- Materials
Abstract:
Objective: To study the effect of micheliolide (MCL) on the sensitivity of colorectal cancer cells to oxaliplatin (OxP) and its possible mechanism.Methods: HCT116 and LoVo cells were treated with 2 μmol/L MCL and 100 μmol/L OxP alone or in combination. The cell viability and colony forming ability in vitro were detected by CCK-8 and plate cloning formation assay, respectively. After being transfected with GFP-LC3 lentivirus, HCT116 cells were respectively treated with 2 μmol/L and 5 μmol/L MCL for 24 h. The aggregation of autophagy bodies in HCT116 cells induced by MCL was observed under fluorescence microscope. The effects of MCL on the expressions of LC3B-Ⅰ, LC3B-Ⅱ, p62 and STAT3 were detected by WB assay; the molecular docking model of MCL and STAT3 was constructed by Autodock version.Results: After the treatment of 2 μmol/L MCL combined with 100 μmol/L OxP, the activity of HCT116 and LoVo cells as well as the colony forming ability of HCT116 cells significantly decreased (all P < 0.01). After HCT116 cells were treated with 2 and 5 μmol/L MCL, the autophagy rate of cells in the treatment groups was significantly higher than that of the control group (all P < 0.01), the LC3B Ⅱ/Ⅰ ratio was 3.25 and 5.78 times that of the control group, the expression level of p62 was 25.5% and 9.8% of the control group, and the phosphorylation level of STAT3 was 2.18 and 3.87 times that of the control group. Molecular docking results showed that MCL might directly bind to STAT3 protein in vivo.Conclusion: MCL may enhance the sensitivity of colorectal cancer cells to OxP by promoting autophagy through STAT3 pathway.
Keywords:
Project Supported:
Project supported by the Key Projects of Tianjin Science and Technology Support Plan (No. 19YFZCSY00420), the Major Special Projects of Science and Technology for Prevention and Control of Major Diseases in Tianjin (No. 18ZXDBSY00040), the Tianjin Health and Family Planning Commission Grant (No. 2017057, No. 2014kZ053, No. 16KG154), and the Open Research Foundation of State Key Laboratory of Medicinal Chemical Biology (Nankai University) (No. 2018094)
Clc Number:
R735.3；R730.54；R730.53
