Celastrus orbiculatus extracts induce apoptosis and inhibit invasion by targeting the maspin gene in human gastric adenocarcinoma cells.

Abstract

Celastrus orbiculatus Thunb. has been used as a remedy against cancer and inflammatory diseases for thousands of years in China. Maspin is expressed in normal cells and downregulated in prostate tumor cells. The underlying mechanisms between C. orbiculatus extract (COE) and maspin remain unclear. In the present study, 3 target-specific 19–25 nucleotide maspin small interfering RNAs were designed and synthesized to knockdown maspin expression. The effects of COE on MGC-803/maspin− cell proliferation were evaluated by the MTT assay. Apoptosis was measured by flow cytometry. Invasive activity was measured with the Transwell assay and the associated molecular mechanisms were assessed by western blot analysis. The results demonstrated that COE significantly promoted the expression of maspin (P<0.01) to induce apoptosis and inhibit invasion and migration in MGC803 cells. The expression levels of phosphorylated (p)-p38 mitogen-activated protein kinase (MAPK), phospho-extracellular regulated protein kinase (Erk), B cell lymphoma-2-associated X protein and caspase-3 were increased in the MGC-803/maspin− cells in a dose-dependent manner. The Erk, B-cell lymphoma 2, p-Akt, Akt and p-mechanistic target of rapamycin (mTOR) protein in MGC-803/maspin− cells were reduced in a dose-dependent manner. This indicated that COE may inhibit invasion and migration through phosphoinositide 3-kinase/Akt/mTOR and MAPK signaling pathways in MGC-803/maspin− cells. In conclusion, COE has the ability to improve the expression of maspin to induce apoptosis and inhibit invasion and migration in human gastric adenocarcinoma cells.