Aloin inhibits lactate-induced proliferation and migration of gastric cancer cells by downregulating HMGB1 expression. - GreenMedInfo Summary
[Aloin inhibits lactate-induced proliferation and migration of gastric cancer cells by downregulating HMGB1 expression].
Nan Fang Yi Ke Da Xue Xue Bao. 2021 Nov 20 ;41(11):1700-1706. PMID: 34916197
T Cai
OBJECTIVE: To assess the inhibitory effects of aloin on lactate-induced gastric proliferation and migration of cancer cells and explore the underlying molecular mechanism.
METHODS: Gastric cancer BGC-823 cells were treated with aloin, lactate or the combination of lactate and different doses of aloin. EdU assay was used to detect the proliferation of BGC-823 cells, and colony formation ability of the cells was evaluated with colony forming assay; wound healing and Transwell assays were used to detect the changes in migration ability of the treated cells. The expression levels of cyclin D1, cyclin E1, PCNA, N-cadherin, E-cadherin, MMP-2, MMP-9 and HMGB1 were determined using Western blotting, and ELISA was performed to detect HMGB1 release. HMGB1 expression was knocked down in BGC-823 cells using RNA interference technique, and the effects of HMGB1 knockdown on proliferation and migration of the cells stimulated with lactate for 24 h were examined using EdU and wound healing assays.
RESULTS: Aloin treatment significantly inhibited lactate-induced proliferation of gastric cancer cells, lowered the colony forming ability of lactate-treated cells, and suppressed lactate-induced migration of the cells. Treatment with lactate obviously up-regulated the expressions of cyclin D1, cyclin E1, PCNA, N-cadherin, MMP-2, MMP-9 and HMGB1, which were significantly inhibited by aloin; aloin significantly reversed inhibition of E-cadherin and blocked the release of HMGB1 in lactate-treated cells. BGC-823 cells with HMGB1 knockdown, as compared with the cells transfected with the negative control plasmid, showed significantly lowered proliferation and migration abilities following lactate treatment.
CONCLUSION: Aloin inhibits lactate-induced proliferation and migration of gastric cancer cells by down-regulating the expression and release of HMGB1 and the expressions of proliferation- and migration-related proteins.