The effects and mechanism of α‐mangostin on chemosensitivity of gastric cancer cells

Abstract

Abstract This work investigated the effect of α‐mangostin (α‐M) on gastric cancer (GC) cell chemoresistance and its underlying mechanisms. Different concentrations of α‐M and CDDP were applied to treat GC cells (SGC7901) and CDDP‐resistant GC cells (SGC7901/CDDP) for 24 or 48 h. CCK‐8 assays were used to measure the inhibitory effect of CDDP or α‐M on SGC7901 and SGC7901/CDDP cells as well as the half‐maximal inhibitory concentrations (IC50) of α‐M for SGC7901 and SGC7901/CDDP cells. The optimal concentration and induction time of CDDP or α‐M were determined. SGC7901/CDDP cells were treated with CDDP or/and α‐M, where some of them were transfected with pcDNA3.1 or pcDNA3.1‐EBI3. Cell proliferation and apoptosis were assessed as well as the levels of EBI3, STAT3, p‐STAT3, autophagy‐related proteins, and apoptosis‐related proteins. CDDP inhibited SGC7901 cell proliferation in a dose‐dependent manner. The IC50 of α‐M for SGC7901 cells was 12.86 μM and that for SGC7901/CDDP cells was 13.69 μM. The optimal concentrations of CDDP and α‐M for SGC7901/CDDP cells were 2 and 15 μM, respectively, and the optimal time was 48 h. The SGC7901/CDDP cells in the CDDP+/α‐M+ group had elevated inhibition of proliferation and apoptosis rates. Western blot analysis revealed enhanced levels of LC3‐II/I and Beclin1, reduced p62 level, decreased Bcl2 level, and increased levels of Bax and cleaved caspase‐3/9. The EBI3/STAT3 pathway was implicated in the effect of α‐M on SGC7901/CDDP cell development. α‐M increases the chemosensitivity of GC cells by facilitating autophagy and inactivating the EBI3/STAT3 pathway.

Keywords

• autophagy
• chemosensitivity
• gastric cancer
• proliferation
• α‐mangostin