Antitumor activity of integrin αVβ3 antibody conjugated-cationic microbubbles in liver cancer.

Abstract

BackgroundThe overexpression of integrin αVβ3 in hepatocarcinoma (HCC) promotes tumor progression, metastasis, and clinical staging. Thus, the inhibition of integrin αVβ3 might be potentially effective as an anti-cancer agent in HCC.MethodsIn this study, we aimed to investigate the antitumor effect of integrin αVβ3 antibody conjugated cationic microbubbles (CMBs) in HCC model. By conjugating with integrin αVβ3 antibody with non-targeting CMBs, CMBsαvβ3 was constructed. The antitumor effect of CMBsαvβ3 was evaluated in HepG2 cells in vitro and in HepG2 xenograft mice models. Bcl-2, p53 and CD31 mRNA level, and caspase-3 activity were examined in xenograft tumors. Cell proliferation assay and scratch test were performed to evaluate the anti-migrant effect of CMBsαvβ3 in vitro.ResultsCMBsαvβ3 could specifically target to HCC HepG2 cells and improve pEGFP-KDRP-CD/TK plasmid transfection efficiency. In HepG2 xenograft mice models, CMBsαvβ3 treatment significantly suppressed tumor weights and volumes. CMBsαvβ3 treatment suppressed Bcl-2 and p53 mRNA level in tumors. In HepG2 cells, CMBsαvβ3 significantly impaired wound healing and inhibited cell proliferation. Moreover, when combined with CD/TK double suicide gene transfection and 5-FC/GCV treatment, caspase-3 was activated and the cell proliferation was tremendously inhibited.ConclusionsCMBsαvβ3 not only suppresses cell migration and proliferation, but also facilitates 5-FC/GCV plus CD/TK double suicide gene-induced apoptotic cell death. CMBsαvβ3 is a promising gene delivery agent with potential anti-tumor activity itself.