Quercetin Enhances Cisplatin Sensitivity of Human Osteosarcoma Cells by Modulating microRNA-217-KRAS Axis

Abstract

Quercetin can suppress osteosarcoma cell growth and metastasis. However, other effects of quercetin on osteosarcoma remain largely unknown. This research aims to evaluate the effects of quercetin in combination with cisplatin as treatment for osteosarcoma and investigate its regulatory mechanism. Cell viability and apoptosis in 143B cell line were determined after treatment with quercetin and/or cisplatin. RT-PCR and Western blot analysis were performed to determine the RNA or protein expression levels. Moreover, transwell assay was used to evaluate metastasis. Furthermore, rescue experiments were performed to investigate the potential regulatory mechanism of the treatment. Results showed that quercetin with concentration that was equal to or greater than 10 μM inhibited 143B proliferation, while 5 μM quercetin enhanced the cisplatin sensitivity of 143B cells. Expression of miR-217 was upregulated after quercetin and/or cisplatin treatment, while its target KRAS was downregulated both at mRNA and protein levels. MiR-217 knockdown led to the loss of enhanced cisplatin sensitivity while miR-217 overexpression showed the opposite effects, indicating that quercetin regulated cisplatin sensitivity by modulating the miR-217-KRAS axis. In conclusion, 5 μM quercetin enhanced the cisplatin sensitivity by modulating the miR-217-KRAS axis. This finding suggests that quercetin may be administered with cisplatin to improve the treatment for osteosarcoma.

Basic Studies on Chemopreventive Properties of Quercetin and Curcumin and Other Plant-origin Compounds in Ovarian Cancer Cells – A Mini-review

“…These results are with the trend of studies indicating that some microRNAs, including the miR-145, are downregulated in ovarian cancer [65,66], and that cancer cells growth inhibition caused by quercetin may be correlated with the modulation of several miRs expression of [60,63,67,68].…”

Quercetin‐mediated regulation of signal transduction cascades and microRNAs: Natural weapon against cancer

“…NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells suppressed Cr(VI)-mediated transformation into malignant cells. 31 Quercetin dose-dependently stimulated expression of miR-145 in the A2780 and SKOV-3 cells. 26 GABARAPL1 or autophagy-related protein 8 (Atg8) is reportedly involved in the formation of autophagosomal membranes.…”

“…C, Quercetin also efficiently upregulated miR-217 and miR-200b-3p. 30 Quercetin was noted to improve cisplatin sensitivity of osteosarcoma cells via upregulation of miR-217 in 143B cells 31 (shown in Figure 2). Likewise, Cr (VI)-mediated malignant transformation was remarkably reduced in PDCD4 overexpressing BEAS-2B cells.…”

The effect of quercetin on microRNA expression: A critical review

“…Zhang et al 78 tested the effect of quercetin on cisplatin treatment in an osteosarcoma model. They used the 143B cell line and recognized that miR-217 is partially responsible for quercetin-mediated sensitivity of cells to cisplatin.…”