Synergistic effect of oxaliplatin and nanocurcumin in dendrosomal carrier to inhibits ovarian cancer cells invasion and metastasis through the long non-coding RNA MEG3

Abstract

Abstract Background: Ovarian cancer (OC) is a common female cancer with a high mortality rate. Maternally Expressed Gene 3 (MEG3) is a long non-coding RNA (lncRNA) located on chromosome 14q32.3 and act as an anti-tumor factor in various cancers. In this study we aimed to determine the role of siRNA–mediated MEG3 knockdown under dendrosomal nanocurcumin (DNC) and Oxaliplatin (OXA) treatment on ovarian cancer cell lines, also the expression levels of cancer-associated gene of Bcl-2, BAX, MMP-2 and MMP-9.Methods: We performed the MTT assay, flow cytometry for cell cycle analysis and Annexin V-FLUOS approach to evaluate the apoptosis, transwell migration and invasion assay in ovarian cancer cell lines. The expression analysis of lncRNA MEG3 and Bcl-2, BAX, MMP-2 and MMP-9 genes was also done using real-time PCR. Results: As result, we found MEG3 expression was significantly increased in two cell lines while it was in a time-dependent manner with OXA (24h and 48h) (P <0.01) and DNC (24h and 48h) (P <0.001) in OVCAR3 cell line. Also, siRNA-meditated MEG3 could significantly suppress many aspects of DNC and OXA anticancer effects in ovarian cancer cell lines. Real time analysis data demonstrated the increased expression of MMP-2 only in DNC (P <0.01) and combination treatment (P <0.001) and increased MMP-9 expression level only in OXA treatment after MEG3 downregulation (P <0.01).Conclusion: The findings of the current study illustrate MEG3 knockdown potentially can affect anti-cancer effects of DNC treatment in migration and invasion of ovarian cancer cell lines by change the expression levels of metastasis-associated genes MMP-2 and MMP-9. Then, it seems DNC and OXA combination treatment act as novel and efficient therapy in ovarian cancer, also MEG3 as a potential biomarker and therapeutic target for drug –resistance ovarian cells.