Stellera chamaejasme extract against multidrug resistance of breast cancer cell line MCF-7.
10.19540/j.cnki.cjcmm.20230103.701
- Author:
Xi-He CUI
1
;
Rui ZENG
1
;
Yuan-Long ZANG
1
;
Qing YANG
1
;
Xiao-Xin ZHU
1
;
Ya-Jie WANG
1
Author Information
1. Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
- Publication Type:Journal Article
- Keywords:
Stellera chamaejasme extract;
apoptosis;
autophagy;
breast cancer;
multidrug resistance
- MeSH:
Humans;
Female;
Breast Neoplasms/metabolism*;
MCF-7 Cells;
Caspase 3/metabolism*;
Caspase 9/metabolism*;
Beclin-1/pharmacology*;
Apoptosis;
Proto-Oncogene Proteins c-bcl-2/metabolism*;
Cell Line, Tumor;
Drug Resistance, Neoplasm;
Cell Proliferation
- From:
China Journal of Chinese Materia Medica
2023;48(9):2360-2367
- CountryChina
- Language:Chinese
-
Abstract:
This study explored the effect and underlying mechanism of Stellera chamaejasme extract(SCE) on multidrug resistance of breast cancer. The chemotherapy-sensitive breast cancer cell line MCF-7 and adriamycin(ADR)-resistant cell line MCF-7/ADR were used as experimental subjects. MTT assay was used to detect cell proliferation activity. Pi staining was used to detect the cell cycle. 4',6-Diamidino-2-phenylindole, dihydrochloride(DAPI) staining and flow cytometry were used to detect apoptosis. Dansylcadaverine(MDC) staining and GFP-LC3B-Mcherry adenovirus transfection were used to detect autophagy. The protein expression of Bcl-2, Bax, caspase-9, caspase-3, LC3B, p62, and Beclin-1 was detected by Western blot. The results showed that SCE could significantly inhibit the proliferation of both sensitive and resistant breast cancer cell lines. The drug resistance factor was 0.53, which was significantly lower than 59 of ADR. Meanwhile, the proportion of sensitive/resistant cells in the G_0/G_1 phase increased significantly after SCE treatment. In addition, DAPI staining showed that a series of apoptosis phenomena such as nuclear pyknosis, staining deepening, and nuclear fragmentation appeared in sensitive/resistant cell lines after SCE administration. Moreover, the results of flow cytometry double staining showed that the proportion of apoptotic cells in sensitive/resistant cell lines increased significantly after SCE administration. Besides, Western blot showed that the protein expression levels of caspase-3, caspase-9, and Bcl-2 significantly decreased and the expression level of Bax protein significantly increased in both breast cancer cell lines after SCE administration. Furthermore, SCE could also increase the positive fluorescent spots after MDC staining and yellow fluorescent spots after GFP-LC3B-mcherry transfection, and up-regulate the expression levels of autophagy-related proteins LC3B-Ⅱ, p62, and Beclin-1 in breast cancer cells. In summary, SCE may play the role of anti-multidrug resistance by blocking the cell cycle of breast cancer multidrug-resistant cells, blocking autophagy flow, and ultimately interfering with the apoptosis resistance of drug-resistant cells.
