Antitumor activity of integrin α_Vβ₃ antibody conjugated-cationic microbubbles in liver cancer

The overexpression of integrin α_Vβ₃ in hepatocarcinoma (HCC) promotes tumor progression, metastasis, and clinical staging. Thus, the inhibition of integrin α_Vβ₃ might be potentially effective as an anti-cancer agent in HCC.

In this study, we aimed to investigate the antitumor effect of integrin α_Vβ₃ antibody conjugated cationic microbubbles (CMBs) in HCC model. By conjugating with integrin α_Vβ₃ antibody with non-targeting CMBs, CMBs_αvβ3 was constructed. The antitumor effect of CMBs_αvβ3 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 CMBs_αvβ3 in vitro.

CMBs_αvβ3 could specifically target to HCC HepG2 cells and improve pEGFP-KDRP-CD/TK plasmid transfection efficiency. In HepG2 xenograft mice models, CMBs_αvβ3 treatment significantly suppressed tumor weights and volumes. CMBs_αvβ3 treatment suppressed Bcl-2 and p53 mRNA level in tumors. In HepG2 cells, CMBs_αvβ3 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.

CMBs_αvβ3 not only suppresses cell migration and proliferation, but also facilitates 5-FC/GCV plus CD/TK double suicide gene-induced apoptotic cell death. CMBs_αvβ3 is a promising gene delivery agent with potential anti-tumor activity itself.