Overexpression of NDRG2 promotes the therapeutic effect of pazopanib on ovarian cancer.

Abstract

Objectives: Ovarian cancer is the second commonly seen cancer in the US, patients with ovarian cancer are commonly diagnosed in the advanced stage. Pazopanib is an inhibitor of multiple tyrosine kinases and has been approved in treatment for carcinoma by FDA. N-myc downstream-regulated gene 2 (NDRG2) has been regarded as a cancer suppressor gene and presented an inhibition effect in cancer proliferation, invasion, and migration.

Design: NDRG2 was overexpressed or inhibited in SKOV-3 cells, then experiments were performed to detect the apoptosis of cells. The expression or secretion of pro-cancer molecules was detected. And the expression of apoptosis-related proteins and the ASK1/JNK1 signaling pathway was detected.

Methods: The NDRG2 overexpression and inhibition model was firstly constructed in SKOV-3 cells, the apoptotic cells were detected using flow cytometry. The expression of cellular metastasis genes was detected using the qPCR method. The angiogenesis factors was detected using the ELISA method. Expression of each target protein was detected using western blotting analysis.

Results: NDRG2 overexpression and inhibition model were constructed in the SKOV-3 cell line, overexpression of NDRG2 enhanced the effect of pazopanib on inhibition of the expression of metastasis-related molecules and angiogenesis-related factors. The apoptosis process of cells was also enhanced after overexpression of NDRG2, and these effects were regulated by the activation of the ASK1/JNK1 signaling pathway.

Limitations: The effect of NDRG2 in animal models and more cell lines needs to be explored in further study.

Conclusions: NDRG2 might be a therapeutic target in treatment for ovarian cancer.