Small interfering RNA expression vector targeting hypoxia-inducible factor 1 alpha inhibits tumor growth in hepatobiliary and pancreatic cancers

Hepatobiliary and pancreatic carcinomas are hypovascular tumors that can proliferate under hypoxic conditions. Recent reports have demonstrated that hypoxia-inducible factor 1 alpha (HIF1 alpha) plays an important role in the survival of these cancers. Given these findings, the inhibition of the HIF1 alpha pathway might prove to be a powerful tool in the treatment of these cancers. To inhibit HIF1 alpha expression, we used small interference RNA ( siRNA) expression vectors in this study. The transient transfection of siRNA expression vectors significantly reduced both HIF1 alpha mRNA levels (13% of control) and protein levels (41% of control) and significantly inhibited the growth of cancer cell lines (P < 0.05). VEGF, Glut1, and aldorase A expressions were also significantly reduced by transfection with these vectors (P < 0.05), and we found that these vectors induced apoptosis but not cell cycle arrest. In a subcutaneous tumor model using nude mice, transfected MIA PaCa-2 cells, stably expressing siRNAs, barely formed tumors compared to control (P < 0.05). This study thus demonstrates the usefulness of siRNA expression vector in targeting HIF1 alpha and points to a potential clinical role in the treatment of pancreatic and hepatobiliary carcinomas.