Melatonin inhibits growth and metastasis of MDA-MB-231 breast cancer cells by activating autophagy.
10.12122/j.issn.1673-4254.2022.02.16
- Author:
Dao Qiu WU
1
;
Yi ZHANG
1
;
Hong Ting TANG
1
;
Juan YANG
1
;
Meng Xing LI
2
;
Hong Lin LIU
3
;
Qin Shan LI
1
Author Information
1. Department of Clinical Biochemistry, School of Medical Laboratory Science, Guiyang 550004, China.
2. Department of Hematology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.
3. Institute of Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing 100000, China.
- Publication Type:Journal Article
- Keywords:
breast cancer;
growth;
melatonin;
metastasis
- MeSH:
Autophagy;
Autophagy-Related Proteins/metabolism*;
Breast Neoplasms;
Cell Line, Tumor;
Female;
Humans;
Melatonin/pharmacology*
- From:
Journal of Southern Medical University
2022;42(2):278-285
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the effects of melatonin on the growth and metastasis of MDA-MB-231 breast cancer cells and explore the mechanism.
METHODS:MDA-MB-231 cells were treated with 1, 3 or 5 mmol/L melatonin, and the changes in cell proliferation were examined using CCK-8 assay. Colony-forming assay and wound healing assay were used to assess the effects of melatonin treatmnent on colony-forming ability and migration of the cells. Flow cytometry and immunofluoresnce assay were employed to examine apoptosis and positive staining for autophagy-related proteins in the cells treated with 3 mmol/L melatonin. The effects of melatonin treatment alone or in combination with 3-methyladenine (3-MA) on the expressions of the proteins associated with autophagy (LC3, P62 and Beclin1), apoptosis (Bcl2 and Bax) and epithelial-mesenchymal transition (E-cadherin and Snail) were examined with Western blotting.
RESULTS:Melatonin treatment significantly inhibited the proliferation of breast cancer cells in a concentration- and time-dependent manner (P < 0.05), suppressed colony-forming ability and migration (P < 0.01), and promoted apoptosis of the cells (P < 0.01). Melatonin treatment alone significantly increased the expressions of Bax (P < 0.05), E-cadherin, LC3-II/LC3-I, and Beclin1 and lowered the expressions of Bcl2 (P < 0.05), Snail, P62 (P < 0.05), and Bcl2/Bax ratio (P < 0.01) in the cells, and caused enhanced positive staining of Beclin1 protein and attenuated staining of P62 protein. Compared with melatonin treatment alone, melatonin treatment combined with 3-MA significantly decreased the expressions of Beclin1 (P < 0.001), LC3-II/LC3-I (P < 0.05), Bax (P < 0.01), and E-cadherin (P < 0.001) and increased the expressions of Bcl2 (P < 0.05), Snail, and Bcl2/Bax ratio (P < 0.01).
CONCLUSION:Melatonin can induce autophagy of MDA-MB-231 breast cancer cells to inhibit cell proliferation and metastasis and promote cell apoptosis, and suppressing autophagy can weaken the inhibitory effect of melatonin on the growth and metastasis of breast cancer cells.
