Hydroxygenkwanin suppresses proliferation, invasion and migration of osteosarcoma cells via the miR‑320a/SOX9 axis

Abstract

Hydroxygenkwanin (HGK) has an anticancer effect in a variety of tumors, but its role in osteosarcoma has not been explored. The purpose of the present study was to investigate the therapeutic effect of HGK on osteosarcoma and its specific molecular mechanism. Osteosarcoma cells (MG-63 and u2oS) treated with various concentrations of HGK were assigned to the treatment group. MTT, clone formation, wound healing and Transwell assays were performed to assess the viability, proliferation, migration, and invasion of MG-63 and u2oS cells. rT-qPcr was conducted to quantify the expression levels of of microRNA (miR)-320a and SRY-box transcription factor 9 (SOX9) in MG-63 and U2OS cells. The binding sites of miR-320a and SOX9 were predicted by star-Base database, and verified using the dual-luciferase reporter assay. The expression levels of SoX9 and eMT-related proteins (n-cadherin, e-cadherin and vimentin) were detected by western blot analysis. HGK inhibited cell proliferation, migration, invasion, but promoted the expression of miR-320a in MG-63 and U2OS cells. Downregulation of miR-320a reversed the effects of HGK on proliferation, migration and invasion of MG-63 and U2OS cells, while upregulation of miR-320a had the opposite effect. HGK inhibited the expression of SoX9 by promoting the expression of miR-320a. Upregulation of SOX9 could partially reverse miR-320a-induced migration and invasion of MG-63 and U2OS cells. In addition, upregulation of miR-320a promoted E-cadherin expression and inhibited the expression of n-cadherin and vimentin, and the effect of miR-320a was also reversed by SOX9. In conclusion, HGK inhibited proliferation, migration and invasion of MG-63 and U2OS cells through the miR-320a/SOX9 axis.

Carbonic Anhydrase Inhibitors Induce Ferroptosis through Inhibition of AKT/FTH1 Signaling in Ewing Sarcoma Tumor Cells

“…In fact, considering the high degree of vimentin protein expression in primary ES cells (Supplemental Figure S3) and the direct Pearson correlation between CAII and vimentin, we suggest that ES cells may rely on vimentin for adhesion and tumor proliferation. This hypothesis can be further supplemented by similar findings previously reported for other cancer cell types [39,40]. Overall, our research indicates that the accumulation of an acidic metabolic state due to treatment with CA inhibitors may render ES cells vulnerable to ferroptosis inducers, especially in the presence of FTH1 modulators [30,41,42].…”

Deciphering chemoresistance in osteosarcoma: Unveiling regulatory mechanisms and function through the lens of noncoding RNA

“…The tyrosine kinase inhibitor Apatinib, a targeted medication for OS, may have an antitumor effect by activating the LINC 00261/miR‐620/PTEN axis (Han et al, 2021). Furthermore, it has been demonstrated that a number of naturally occurring active substances, including Arbutin, Hydroxygenkwanin, Rhizoma Paridis saponins, Magnoflorine, and Cinnamtannin B‐1, inhibit the development and metastasis of OS by controlling the expression of tumor suppression‐related miRNAs to regulate target genes (Dong et al, 2022; Jia et al, 2023; Wang, Shang, et al, 2020; Wang, Wang, et al, 2021; Yao et al, 2022). Magnoflorine, in particular, increases the susceptibility of OS cells to DDP by controlling the miR‐410‐3p/HMGB1/NF‐κβ pathway (Wang, Shang, et al, 2020).…”