CRABP2 affects chemotherapy resistance of ovarian cancer by regulating the expression of HIF1α.

ABSTRACT

Ovarian cancer is the most lethal malignancy among gynecologic cancers, and primary and secondary chemotherapy resistance is one of the important reasons for poor prognosis of ovarian cancer patients. However, the specifics of resistance to chemotherapy in ovarian cancer remain unclear. Herein, we find that the expression level of cellular retinoic acid binding protein 2 (CRABP2) is up-regulated in drug-resistant ovarian cancer tissues and cell lines, and the expression levels of CRABP2 in epithelial ovarian cancer tissues are closely related to tumor clinical stage and patients' prognosis, suggesting that CRABP2 plays an important role in the progression of ovarian cancer and the corresponding ability of tumor to chemotherapy. With the in-depth study, we demonstrates that CRABP2 is related to the high metabolic activity in drug-resistant cells, and all-trans retinoic acid exacerbates this activity. Further molecular mechanism exploration experiments show that CRABP2 not only up-regulates the expression level of HIF1α, but also increases the localization of HIF1α in the nucleus. In drug-resistant ovarian cancer cells, knocking down HIF1α can block the resistance of CRABP2 to chemotherapy drugs in ovarian cancer cells. Taken together, our findings suggest for the first time that CRABP2 affects chemotherapy resistance of ovarian cancer by regulating the expression of HIF1α. This study provides a possible molecular mechanism for drug resistance and a possible molecular target for clinical treatment of ovarian cancer.