Effect of hypoxia inducible factor-1 antisense oligonucleotide on liver cancer

Hepatocellular carcinoma (HCC) is one of the most frequent primary malignancies of the liver and is resistant to anticancer drugs. Hypoxia is a master cause of tumor resistance to chemotherapy. Hypoxia-inducible factor-one alpha (HIF-1α) plays a key role in the adaptive responses to hypoxic environments. HIF-1α is constitutively up-regulated in several tumor types might thus be implicated in tumor therapy resistance. We hypothesized that disruption of HIF-1α pathway could reverse the hypoxia-induced resistance to chemotherapy. In this report, we prepared DOTAP (a liposome formulation of a mono-cationic lipid N-[1-(2,3-Dioleoyloxy)]- N,N,N-trimethylammonium propane methylsulfate in sterile water) cationic liposomes containing an antisense oligonucleotide (AsODN) against HIF-1α. Gene transfer of antisense HIF-1α was effective in suppressing tumor growth, angiogenesis, and cell proliferation, and inducing cell apoptosis. Our results suggested that antisense HIF-1α therapy could be a therapeutic strategy for treating HCC.