Study of RNA Interference Targeting NET-1 Combination with Sorafenib for Hepatocellular Carcinoma Therapy In Vitro and In Vivo

Abstract EN

The aim of this study is to explore the inhibitory effects of RNA interference (RNAi) targeting NET-1 or combined with sorafenib on HCC in vitro and in vivo and the possible underlying mechanisms.

The expressions of NET-1 mRNA and protein were detected by RT-QPCR and western blot.

The ability of proliferation was determined by CCK-8 assay.

Apoptosis was examined by flow cytometry (FCM).

Abilities of migration and invasion were measured by scratch-wound assay and transwell assay.

MHCC97H cells with stable transfection of NET-1shRNA were injected subcutaneously to prepare nude mice model of HCC and Caspase-3, Caspase-8, and Caspase-9 mRNAs of tumor tissues in different groups were examined.

NET-1 mRNA and protein were reduced sharply in MHCC97H cells transfected with NET-1shRNA.

The abilities of proliferation and migration were inhibited and apoptosis was promoted in either NET-1shRNA or sorafenib as compared with untreated cells in vitro and in vivo (P<0.05).

The mRNA levels of caspase-3, caspase-8, and caspase-9 of tumor tissues were reduced in different treatment groups compared with untreated group, particularly in combination group.

(P<0.05).

The combination NET-1shRNA with sorafenib dramatically enhanced the effects of sorafenib antitumor ,which may involve in blocking ras signaling pathway and stimulating apoptotic pathways simultaneously.