Outpatient Department, Gansu Provincial Hospital, Lanzhou 730000, P.R. China.
Department of Plastic Surgery, General Hospital of Guangzhou Military Command, Guangzhou 510010, P.R. China.
Int J Oncol. 2015 Jan;46(1):215-22. doi: 10.3892/ijo.2014.2715. Epub 2014 Oct 21.
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.
虽然 HIF-1α 被认为是癌症治疗药物开发的一个有吸引力的靶点，但与其他转录因子一样，它也被认为是“不可成药的”。诱饵方法是一类新的抗基因策略，可用于调节内源性转录因子的功能。在这里，我们设计了一种 HIF-1α 诱饵寡脱氧核苷酸（ODN），并测试了它对 HIF-1α 功能的影响。我们发现 HIF-1α 诱饵 ODN 能够有效地进入细胞。此外，这些诱饵 ODN 可以显著阻断 VEGFA 的表达，VEGFA 是 HIF-1α 的一个已知靶向基因，这表明 HIF-1α 诱饵 ODN 可以抑制 HIF-1α 的功能。更重要的是，HIF-1α 诱饵 ODN 诱导 MDA-MB-231 乳腺癌细胞凋亡和细胞周期停滞。总之，HIF-1α 诱饵 ODN 可以抑制 HIF-1α 的功能并诱导癌细胞凋亡。因此，应该进一步修饰 HIF-1α 诱饵 ODN 以提高其在体内的生物学活性。
