Swainsonine represses glioma cell proliferation, migration and invasion by reduction of miR-92a expression

Background: Swainsonine is a natural indolizidine alkaloid, its anti-tumor activity has been widely reported in varied cancers. This study aimed to investigate whether Swainsonine exerted anti-tumor impact on Glioma cells, likewise uncovered the relative molecular mechanisms.

Methods: After administration with diverse concentrations of Swainsonine, cell growth, migration and invasion in U251 and LN444 cells were appraised by the common-used CCK-8, BrdU, flow cytometry and Transwell assays. MiR-92a mimic, inhibitor and the correlative NC were transfected into U251 and LN444 cells, and assessment of miR-92a expression was by utilizing qRT-PCR. Functions of miR-92a in above-mentioned cell biological processes were analyzed again in Swainsonine-treated cells. The momentous proteins of cell cycle, Apoptosis and PI3K/Akt/mTOR pathway were ultimately examined by western blot.

Results: Swainsonine significantly hindered cell proliferation through decreasing cell viability, declining the percentage of BrdU cells, down-regulating CyclinD1 and up-regulating p16 expression. Enhancement of percentage of apoptotic cells was presented in Swainsonine-treated cells via activating cleaved-Caspase-3 and cleaved-Caspase-9. Additionally, Swainsonine impeded the abilities of migration and invasion by decreasing MMP-2, MMP-9, Vimentin and E-cadherin. Repression of miR-92a was observed in Swainsonine-treated cells, and miR-92a overexpression overturned the anti-tumor activity of Swainsonine in Glioma cells. Finally, western blot assay displayed that Swainsonine hindered PI3K/Akt/mTOR pathway via regulating miR-92a.

Conclusions: These discoveries corroborated that Swainsonine exerted anti-tumor impacts on Glioma cells via repression of miR-92a, and inactivation of PI3K/Akt/mTOR signaling pathway.