Astragalus polysaccharides decrease proliferation, migration, and invasion but increase apoptosis of human osteosarcoma cells by up-regulation of microRNA-133a

Abstract

Osteosarcoma (OS) has a high incidence, malignity, and frequency of recurrence and metastasis. In this study, we aimed to explore the potential anti-cancer effects of Astragalus polysaccharides (APS) on human OS MG63 cells as well as underlying mechanisms. Viability of MG63 cells was assessed by CCK-8 assay to determine the adequate concentration of APS. Then, effects of APS on MG63 cell proliferation, cell cycle distribution, apoptosis, and migration and invasion were analyzed by BrdU incorporation, PI staining, flow cytometry, and transwell assays, respectively. The expression levels of proteins involved in these physiological processes were assessed by western blot analysis. Afterwards, miR-133a level in APS-treated cells was determined by qRT-PCR, and whether APS affected MG63 cells through regulation of miR-133a was determined. Finally, the activation of c-Jun N-terminal protein kinase (JNK) pathway was detected. We found that APS treatment suppressed the viability, proliferation, migration, and invasion of MG63 cells, as well as induced cell apoptosis. Moreover, APS enhanced the expression of miR-133a in MG63 cells. Knockdown of miR-133a reversed the APS treatment-induced MG63 cell proliferation, migration and invasion inhibition, as well as cell apoptosis. Furthermore, APS inactivated JNK pathway in MG63 cells. Knockdown of miR-133a reversed the APS treatment-induced inactivation of JNK pathway in MG63 cells. To conclude, APS repressed proliferation, migration, and invasion while induced apoptosis of OS MG63 cells by up-regulating miR-133a and then inactivating JNK pathway.

WIN55,212-2-Induced Expression of Mir-29b1 Favours the Suppression of Osteosarcoma Cell Migration in a SPARC-Independent Manner

“…Specifically, we demonstrate here that WIN markedly reduced the migratory ability of osteosarcoma MG63 cells, and this effect was accompanied by a dramatic reduction in the extracellular activity and intracellular levels of MMP2 and MMP9 metalloproteases. Although conflicting data are present in the literature regarding the expression levels of metalloproteases in osteosarcoma cells [31,32], we found that, in our serum-free conditions, both the intracellular levels and extracellular activity of MMP9 were higher than those of MMP2. Fragmentary data in the literature demonstrate that WIN can inhibit the epithelial mesenchymal transition and migration in different cancer cell models [33,34] In an attempt to clarify the mechanism of the anti-migratory effect of WIN in osteosarcoma cells, our study specifically focuses on a possible involvement of the matricellular protein SPARC and a hypothetical role exerted by miR-29b1.…”

Astragalus polysaccharides inhibit ovarian cancer cell growth via microRNA-27a/FBXW7 signaling pathway

“…Several studies have reported that APS exhibits its growth inhibitory effects on cancer cells through modulation of miRNAs [6,15]. Based on the studies reported above, we postulated that APS induced antiproliferative and pro-apoptotic effects in OC through regulation of miRNAs.…”

“…Resveratrol could alter the expressions of many miRNAs in PC-3M-MM2 cells, which may contribute to its anti-tumor property in prostate cancer [23]. A recent study has demonstrated that APS play a tumor suppressive role in human osteosarcoma cells by up-regulation of miR-133a [6]. It is for that reason that we investigated the role of miRNA in the anti-tumor property of APS.…”

“…Astragalus polysaccharides (APS), an active ingredient isolated from the roots of Astragalus membranaceus, has gained considerable attention due to its potent anticancer activities. APS has been shown to be remarkable in inhibiting cell proliferation and inducing apoptosis of human breast cancer and osteosarcoma [5,6]. For example, APS treatment suppressed the tumor growth in mice model of lung cancer [7].…”

A Systematic Review of Phytochemistry, Pharmacology and Pharmacokinetics on Astragali Radix: Implications for Astragali Radix as a Personalized Medicine

“…It was demonstrated that APS could induce the apoptosis of human HCC cells by decreasing the expression of Notch1 [144] (Figure 4⑩). What is more, APS was also proved to repress proliferation, migration and invasion while induced apoptosis of human osteosarcoma MG63 cells by up-regulating miR-133a and then inactivating JNK pathway [145].…”