Hypoxia-induced HIF1α dependent COX2 promotes ovarian cancer progress.

Hypoxia can promote the progression and metastasis of ovarian cancer, while the underlying mechanisms are still unclear. Hypoxia culture or CoCl2 induced-oxygen deprivation condition could promote SKOV3 cells to express cyclooxygenase-2 (COX2). Luciferase assay indicates that hypoxia-inducible factor 1α (HIF1α) could bind directly with the promoter region of COX2 to promote the transcription. COX2 over-expressed SKOV3 cells show up-regulated stemness-related markers expression, proinflammatory gene expression, and increased tumor sphere formation. The inflammatory molecules (interleukin-6, C-X-C motif chemokine ligand 12, interleukin-1B, interleukin-10, and C-C motif chemokine ligand 2) and COX2 expression show positive correlations in the Cancer Genome Atlas data. COX2 over-expression could promote SKOV3 cell proliferation in the subcutaneous tumor model and metastasis in the transfer model. In conclusion, hypoxia-induced HIF-1α mediated COX2 expression could promote the proliferation, inflammation, and metastasis of ovarian cancer.