An Experimental Study Of Dauricine And MiRNA-205-5p In Inhibiting Renal Cell Carcinoma By Regulating The PI3K/Akt Pathway

BackgroundRenal cell carcinoma(RCC),which is derived from the proximal tubules of nephrons,is one of the most common solid cancers.Due to its inherent insensitivity to radiotherapy and chemotherapy,surgery remains the only curative strategy for RCC.Therefore,a novel strategy for treating RCC is urgently needed.This study aims to investigate the effects of dauricine,a bisbenzylisoquinoline alkaloid,in RCC cells and the underlying mechanisms of its action.MethodsThe effects of dauricine on viability,cell cycle distribution and apoptosis in RCC cells were determined in vitro by MTT assay,flow cytometry and nucleosome ELISA assay,respectively.Mechanism studies were performed by analyzing related proteins using western blotting assays.ResultsWe show that dauricine effectively inhibits the viability of four RCC cell lines(786-O,Caki-1,A-498 and ACHN).In addition,dauricine induces cell cycle arrest at the G0/G1 phase in RCC cells.Dauricine also induces apoptosis via the intrinsic pathway,since caspase-9 and caspase-3 but not caspase-8 activation was detected after the treatment.Moreover,dauricine was able to inhibit the PI3K/Akt signaling pathway.ConclusionsOur findings suggest inhibitory effects of dauricine in renal cancer cells and provide a better understanding of its underlying mechanism.Our findings suggest that dauricine could be a potential therapeutic agent for treating RCC.BackgroundMi RNAs(Micro RNAs)have been found involved in the development of various cancers.Mi R-205-5p has been reported dysregulated in various types of human cancer.However,little is known about the role of miR-205-5p in renal cell carcinoma(RCC).The present study was designed to investigate the role of miR-205-5p in RCC.MethodsThe expression of miR-205-5p was measured in RCC tissues and cells by RT-PCR.CCK-8 assay,wound healing and ELISA assay assessed the effects of miR-205-5p on cell growth,migration and apoptosis,respectively.Western blot detected the change of proteins.Bioinformatic analysis and luciferase reporter assay identified the potential target of miR-205-5p.Xenograft mice were used to verify the effect of miR-205-5p in vivo.ResultsMi R-205-5p is downregulated in 25 RCC tissues compared to adjacent normal tissues.Decreased expression of miR-205-5p was associated with poor clinical outcome.In vitro experiments indicated that overexpression of miR-205-5p reduced RCC cells proliferation and migration.It was also found that overexpression of miR-205-5p promoted apoptosis.Moreover,bioinformatic analysis and luciferase reporter assay indicated that miR-205-5p directly targeted the 3'-UTR region of VEGFA,which is important in PI3K/Akt pathway.Further analysis showed that miR-205-5p could negatively regulate the expression of VEGFA.In RCC tissues,miR-205-5p was inversely correlated with the expression of VEGFA.Moreover,overexpression of miR-205-5p could inhibit the RCC growth in vivo in a xenograft mice model.ConclusionsOverall,these findings suggest that miR-205-5p functions as a tumor suppressor in RCC via targeting VEGFA and PI3K/Akt signaling pathway,providing a potential therapeutic target for treatment of cc RCC.