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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. © 2021 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia on behalf of Kaohsiung Medical University.

Citation

Rong-Rong Li, De-Yu Zeng. The effects and mechanism of α-mangostin on chemosensitivity of gastric cancer cells. The Kaohsiung journal of medical sciences. 2021 Aug;37(8):709-717

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PMID: 34003591

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