RETRACTED ARTICLE: Swainsonine represses glioma cell proliferation, migration and invasion by reduction of miR-92a expression

Abstract

BackgroundSwainsonine 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.MethodsAfter 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.ResultsSwainsonine 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.ConclusionsThese discoveries corroborated that Swainsonine exerted anti-tumor impacts on glioma cells via repression of miR-92a, and inactivation of PI3K/AKT/mTOR signaling pathway.Electronic supplementary materialThe online version of this article (10.1186/s12885-019-5425-7) contains supplementary material, which is available to authorized users.

Activation of G protein coupled estrogen receptor prevents chemotherapy-induced intestinal mucositis by inhibiting the DNA damage in crypt cell in an extracellular signal-regulated kinase 1- and 2- dependent manner

“…Cyclin D1 and B1 promote the transformation of G1 → S phase and G2 → M phase in the cell cycle respectively. Decreasing the expression of cyclin D1 and B1 was related with the dysfunction of cell cycle transition and proliferation inhibition, like the BrdU + cells decreasing [ 46 , 47 ]. However, here, the decrease in the numbers of BrdU + and Ki67 + cells following 5-FU treatment was accompanied by a significant increase in the expression of both cyclin D1 and cyclin B1.…”

Modulation of Multiple Signaling Pathways of the Plant-Derived Natural Products in Cancer

“…Piperlongumine (Figure 5) (125), swainsonine (Figure 5) (126), and sinomenine (Figure 5) (127) induce apoptosis and inhibit cancer cell growth through the PI3K/Akt/mTOR pathway, with decreased levels of p-Akt and p-mTOR, as evidenced by the results of Western blot analysis and immunofluorescence. Isoliensinine (Figure 5), matrine, dauricine (Figure 5), and cepharanthine (Figure 5) induce autophagy through the AMPK-TSC2-mTOR signaling pathway, with suppression of mTOR activity (128–130).…”

Biologically active indolizidine alkaloids

“…Subsequent studies explored the in vivo effects of SW on melanoma, 29 Ehrlich ascites carcinoma, 30 colorectal cancer, 31 human liver cancer, 32 lymphoma, 33 and leukemia 34 ; the results showed that all patients obtained good therapeutic effects 30,32,34,35 . The specific mechanisms of action include the following effects (Figure 3): inhibition of α‐mannosidase II, 137,138 promotion of tumor cell apoptosis, 139 enhancement of the immune system, 140 increase of intracellular calcium ion concentration, inactivation of the PI3K/AKT/mTOR signaling pathway, and repression of miR‐92a 141 . As a novel anticancer drug candidate, the biosynthesis of SW has also received attention as recently reviewed 142 …”