Role of Hypoxia-inducible factor-1 alpha and Survivin in colorectal carcinoma progression.

Background And Aims: Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is the main active subunit of HIF-1 that promoted tumor cells survival and critical steps in tumor progression and aggressiveness. The authors aimed to investigate the role of HIF-1 alpha and Survivin in colorectal cancer (CRC) progression.

Materials And Methods: Plasmid expressing small interfering RNA (siRNA) against HIF-1 alpha was constructed and transfected into LS174T cells with Lipofectamine. The LS174T cells were incubated for 24 h under hypoxic condition. The inhibitory effects of siRNA on HIF-1 alpha gene was determined by semiquantitative reverse transcriptase polymerase chain reaction and Western blot. Expression of HIF-1 alpha and Survivin was investigated by immunohistochemistry in colorectal adenocarcinomas tissue microarrays.

Results: HIF-1 alpha and Survivin expressions were markedly downregulated after the siRNA expression vector against HIF-1 alpha was transfected into the LS174T cells. Of the eight adenoma lesions, one case (12.25%) and four cases (50%) were positive for HIF-1 alpha and Survivin, respectively. Of the 69 cases of CRCs, 46 cases (66.7%) and 39 cases (56.5%) were positive for HIF-1 alpha and Survivin, respectively. The positive rate of HIF-1 alpha protein in CRCs was significantly higher than that in colorectal adenoma lesions (P < 0.05). HIF-1 alpha protein expression was significantly higher in patients with stage III than in patients with stage I-II CRCs (P < 0.01). In addition, overexpression of HIF-1 alpha in higher stages of CRCs was found to correlate positively with Survivin levels (P < 0.001).

Conclusions: Our data demonstrate that HIF-1 alpha and Survivin are mostly expressed in invasive CRCs. Inhibition of HIF-1 alpha may lead to exploration of its potential as a diagnostic tool and possibly a target for gene therapy for colorectal carcinoma.