Micheliolide enhances the sensitivity of colorectal cancer cells to oxaliplatin by promoting autophagy
DOI: 10.3872/j.issn.1007-385x.2021.02.003
- VernacularTitle:含笑内酯通过促进自噬增强结直肠癌细胞对奥沙利铂的敏感性
- Author:
QI Chunsheng1, 2
1
,
2
;
ZHANG Qinghuai2
3
;
QI Lin1,
4
;
ZHANG Ping1
4
;
CUI Jifang2
3
;
ZHANG Weihua2
3
;
SU Yanjun3
5
;
ZHANG Chunze2, 4
3
,
6
Author Information
1. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology &Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China;
2. Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, 300121, China;
3. Department of Colorectal Surgery, Tianjin Union Medical Center, Tianjin, 300121, China
4. State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China
5. Clinical Research Center for Cancer of Tianjin City, Key Laboratory of Cancer Prevention and Therapy of Tianjin City, Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China;
6. State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin 300071, China
- Publication Type:Journal Article
- Keywords:
colorectal cancer;
micheliolide;
oxaliplatin;
autophagy;
STAT3
- From:
Chinese Journal of Cancer Biotherapy
2021;28(2):115-120
- CountryChina
- Language:Chinese
-
Abstract:
[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.
- Full text:zgzlswzlzz-2021-2-115.pdf
