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

• Published in: BMC cancer Vol. 19; no. 1; pp. 247 - 10
• Main Authors: Sun, Libo, Jin, Xingyi, Xie, Lijuan, Xu, Guangjun, Cui, Yunxia, Chen, Zhuo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 19-03-2019; BioMed Central; BMC
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Alkaloids; Angiogenesis; Antineoplastic Agents, Phytogenic - pharmacology; Antineoplastic Agents, Phytogenic - therapeutic use; Antitumor agents; Apoptosis; Brain cancer; Cancer; Cancer research; Cancer therapies; Care and treatment; Caspase; Caspase-3; Caspase-9; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Movement - genetics; Cell proliferation; Cell Proliferation - drug effects; Cell Proliferation - genetics; Cell viability; Cholecystokinin; Drug Screening Assays, Antitumor; E-cadherin; Flow cytometry; Gelatinase A; Gelatinase B; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Gene Expression Regulation, Neoplastic - genetics; Genetic aspects; Glioma; Glioma - drug therapy; Glioma - pathology; Glioma cells; Gliomas; Humans; Metastasis; MicroRNA; microRNA-92a; MicroRNAs; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Molecular modelling; Neoplasm Invasiveness - prevention & control; Phosphatidylinositol 3-Kinases - metabolism; PI3K/AKT/mTOR; Proliferation; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Signal transduction; Signal Transduction - drug effects; Signal Transduction - genetics; Swainsonine; Swainsonine - pharmacology; Swainsonine - therapeutic use; TOR protein; TOR Serine-Threonine Kinases - metabolism; Tumors; Vimentin; United States > US; microRNA-92a; PI3K/AKT/mTOR; Proliferation; Glioma; Swainsonine
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-5425-7

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.
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.
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.
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.