Eur Rev Med Pharmacol Sci 2020; 24 (11): 6417-6425

DOI: 10.26355/eurrev_202006_21540

Trichostatin A alleviates the process of breast carcinoma by downregulating LPAR5

Y.-Q. Zheng, X. Miao, J. Li, M.-F. Hu, Y.-S. Zhu, X.-R. Li, Y.-J. Zhang

Department of General Surgery, First Medical Center, PLA General Hospital, Beijing, China. zhangyanjun@301hospital.com.cn


OBJECTIVE: To elucidate the role of histone deacetylase inhibitor Trichostatin A (TSA) in affecting metastasis of breast carcinoma, and its molecular mechanism.

PATIENTS AND METHODS: LPAR5 levels in breast carcinoma tissues and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR), and its expression pattern was further verified in breast carcinoma cell lines. The relationship between LPAR5 and prognosis of breast carcinoma patients was analyzed. After TSA induction (100-400 nmol/L) for 6-48 h, the proliferative and migratory abilities of SKBR3 and MDA-MB-231 cells in overexpressing LPAR5 were examined by cell counting kit-8 (CCK-8), transwell and wound healing assay. By constructing a xenograft model in nude mice, the influences of TSA and LPAR5 on in vivo growth of breast carcinoma were examined.

RESULTS: LPAR5 was upregulated in breast carcinoma samples. High level of LPAR5 predicted higher rates of lymphatic metastasis and distant metastasis, as well as lower overall survival and progression-free survival in breast carcinoma patients. LPAR5 level was dose-dependently downregulated in TSA-induced SKBR3 and MDA-MB-231 cells. In addition, TSA induction dose-dependently declined proliferative ability, and time-dependently attenuated migratory ability in breast carcinoma cells. In vivo overexpression of LPAR5 in nude mice reversed the inhibitory effect of TSA on breast carcinoma growth.

CONCLUSIONS: TSA induction can suppress proliferative and migratory abilities in breast carcinoma by downregulating LPAR5.

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To cite this article

Y.-Q. Zheng, X. Miao, J. Li, M.-F. Hu, Y.-S. Zhu, X.-R. Li, Y.-J. Zhang
Trichostatin A alleviates the process of breast carcinoma by downregulating LPAR5

Eur Rev Med Pharmacol Sci
Year: 2020
Vol. 24 - N. 11
Pages: 6417-6425
DOI: 10.26355/eurrev_202006_21540