Mechanism of HIF-1α promoting proliferation, invasion and metastasis of nasopharyngeal carcinoma by regulating MMP-2 in hypoxic microenvironment.

OBJECTIVE

To explore the mechanism of HIF-1α promoting the proliferation, invasion and metastasis of nasopharyngeal carcinoma cells by regulating the expression of MMP-2.

METHODS

30 nasopharyngeal carcinoma tissues and 30 normal nasopharyngeal epithelial tissues were collected, and the expression of HIF-1α and MMP-2 in the nasopharyngeal carcinoma, normal nasopharyngeal epithelial tissues and their hypoxic environment were systematically analyzed by qRT-PCR and western blot techniques. Lentivirus transfection technology was used to regulate the expression of HIF-1α and MMP-2 genes in the HONE1 cell line under hypoxic environment, and to explore the interaction mechanism of HIF-1α and MMP-2 genes and their role in the proliferation, invasion and metastasis of nasopharyngeal carcinoma. Furthermore, the cytological behavior changes regulated by HIF-1α and MMP-2 genes were further explored by gene chip technology.

RESULTS

The expressions of HIF-1α and MMP-2 in nasopharyngeal carcinoma tissues were significantly higher than those in normal nasopharyngeal epithelial tissues (P < 0.05). Compared with normoxic group, the expression of HIF-1α and MMP-2 in the nasopharyngeal carcinoma cell line HONE1 increased in hypoxic group (P < 0.05). Compared with NC-siRNA group, the expression of HIF-1α in si-HIF-1α group decreased, and the cell proliferation ability and invasion and metastasis ability decreased (P < 0.05). PCR array analysis revealed that the mRNA expressions of FAS, BRCA1, TIMP-1 genes were up-regulated in nasopharyngeal carcinoma HONE1 cells with HIF-1α gene silencing. AKT1, VEGFA, MET, MMP-2, MMP-9 and MTA2 were down-regulated. Compared with NC-siRNA group, the expression of MMP-2 in si-MMP-2 group decreased, and the ability of cell proliferation and invasion and metastasis decreased (P < 0.05).

CONCLUSION

HIF-1α could inhibit the proliferation, invasion and metastasis of nasopharyngeal carcinoma by regulating the expression of MMP-2, thus inhibiting tumor growth. Therefore, HIF-1α and MMP-2 might become important therapeutic targets to inhibit the growth, invasion and metastasis of nasopharyngeal carcinoma.