Glaucocalyxin a prevents hypoxia-induced epithelial-mesenchymal transition in human gastric cancer cells through the PI3K/Akt signaling pathway.

Hypoxia is a frequent occurrence in most solid tumors and associated with multiple cancer progression. Glaucocalyxin A (GLA) has been found to exhibit anti-tumor effect in several types of cancer, except gastric cancer (GC). The present study aimed to evaluate the function of GLA in GC and explore the underlying mechanism under hypoxia condition. Our results showed that GLA suppressed cell viability of MGC-803 cells in both normoxic or hypoxic conditions. MGC-803 cells were more sensitive to GLA in hypoxic condition. GLA attenuated hypoxia-induced migration and invasion of GC cells. Western blot assay proved that GLA elevated E-cadherin expression, as well reduced N-cadherin and vimentin expressions in hypoxia-induced GC cells. Moreover, we also found that GLA suppressed the expression of HIF-1α in both mRNA and protein levels. Furthermore, GLA blocked hypoxia-induced activation of PI3K/Akt pathway in GC cells. Notably, insulin like growth factor 1 (IGF-1), an activator of PI3K/Akt pathway, reversed the effects of GLA on cell migration, invasion and EMT in hypoxia-treated MGC-803 cells. In conclusion, these findings demonstrated that GLA exerted inhibitory effects on cell migration, invasion and epithelial to mesenchymal transition (EMT) the PI3K/Akt signaling pathway in GC cells.