Abstract | BACKGROUND: METHODS: The expression of MUC4 in human gastric cancer tissues was assayed by immunohistochemistry. Then, we performed in vitro cell proliferation and invasion analysis to explore the antitumor effect of ALA using AGS, BGC-823, and MKN-28 cells. To further explore the mechanism of ALA-mediated downregulation of MUC4, we cotransfected human gastric cancer cells with STAT3 siRNA and STAT3 overexpression construct. ChIP assays were carried out to find the relationship between MUC4 and STAT3. RESULTS: We found that the MUC4 gene was strongly expressed in human gastric cancer tissues. Meanwhile, ALA reduced proliferation and invasion of human gastric cancer cells by suppressing MUC4 expression. We also found that STAT3 was involved in the inhibition of MUC4 by ALA. Mechanistically, ALA suppressed MUC4 expression by inhibiting STAT3 binding to the MUC4 promoter region. CONCLUSION: ALA inhibits both proliferation and invasion of gastric cancer cells by suppression of STAT3-mediated MUC4 gene expression.
|
Authors | Yu Yang, Erhu Fang, Jiajun Luo, Hongxue Wu, Yue Jiang, Ying Liu, Shilun Tong, Zhihua Wang, Rui Zhou, Qiang Tong |
Journal | Oxidative medicine and cellular longevity
(Oxid Med Cell Longev)
Vol. 2019
Pg. 3643715
( 2019)
ISSN: 1942-0994 [Electronic] United States |
PMID | 31915505
(Publication Type: Journal Article)
|
Copyright | Copyright © 2019 Yu Yang et al. |
Chemical References |
- Antioxidants
- MUC4 protein, human
- Mucin-4
- Neoplasm Proteins
- STAT3 Transcription Factor
- STAT3 protein, human
- Thioctic Acid
|
Topics |
- Antioxidants
(pharmacology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Gene Expression Regulation, Neoplastic
(drug effects)
- Humans
- Mucin-4
(metabolism)
- Neoplasm Proteins
(metabolism)
- STAT3 Transcription Factor
(metabolism)
- Stomach Neoplasms
(metabolism, pathology)
- Thioctic Acid
(pharmacology)
|