HIF-1α decoy oligodeoxynucleotides inhibit HIF-1α signaling and breast cancer proliferation

Abstract

Although HIF-1α is considered an attractive target for the development of cancer therapies, like other transcriptional factors, it has been regarded as 'undruggable'. The decoy approach is a new class of antigene strategy that can be used to modulate the function of endogenous transcriptional factors. Here, we designed a decoy oligodeoxynucleotide (ODN) and tested its effect on the function of HIF-1α. We found the HIF-1α decoy ODN could efficiently enter into cells. Furthermore, these decoy ODNs can significantly block the expression of VEGFA, a known targeted gene of HIF-1α suggesting that the HIF-1α decoy ODNs can inhibit the function of HIF-1α. More importantly, the HIF-1α decoy ODN induced apoptosis and cell cycle arrest in MDA-MB-231 breast cancer cells. In summary, HIF-1α decoy ODNs can inhibit the function of HIF-1α and induce cancer cell apoptosis. Therefore, HIF-1α decoy ODNs should be further modified to improve their biological activity in vivo.