Abstract 1009: Combination Niraparib and Metformin synergistically inhibits endometrial cancer cell growth and metastasis

Backgroud Endometrial Carcinoma (EC) is the most common gynecological malignancy among women. Even with a favorable prognosis, cure is still elusive with recurrence, chemotherapy resistance and poor outcome. Poly ADP-ribose polymerase inhibitors (PARPi) have been emerged as promising cancer therapeutics, especially for tumors with deficient homologous recombination (HR) repair. Niraparib for example is well established for ovarian cancer. Metformin, an antidiabetic drug, has been reported to be a new adjunctive strategy for different cancer types, including endometrial cancer. While the effect of Niraparib for EC as monotherapy or in combination with Metformin is still unknown. Method Here we used two types of endometrial cancer cell lines Ishikawa and HEC-1B to detect the effect of Niraparib as monotherapy or in combination with Metformin on cell proliferation, apoptosis, invasion and metastasis. The 50% Inhibitory concentration (IC50) was assessed, and transwell, Annexin V staining, clonogenic assay were applied. Also, western blotting was performed to determine the expression of proteins involved, such as Bax, Caspase-3, Bcl-2, p-AKT, RAD51, γ-H2AX and so on. Results Our study demonstrated that Niraparib inhibited endometrial cell growth in both Ishikawa and HEC-1B cell lines with IC50 0.024umol/L and 0.127umol/L separately. The invasion and metastasis were also suppressed. Annexin V staining showed that Niraparib could significantly promoted apoptosis, which was largely enhanced by Metformin combination therapy (p