Effect of Wnt pathway inhibitor on ovarian cancer tumors.

Abstract

e15010 Background: Ovarian cancer (OC) is the fourth most common cancer in women aged 40-54 years. Despite advances in cancer research, no existing methods provide effective early diagnosis and treatment of OC, so the search for new medications is an urgent task. The effectiveness of the XAV-939 pharmacological substance, which inhibits the Wnt signaling pathway, was studied in an orthotopic patient-derived xenograft of human ovarian cancer. Methods: A PDX model was created in 20 female immunodeficient Balb/c Nude mice. A tumor fragment was implanted into the ovary, and the ovary was transposed under the skin to better visualize the xenograft growth. When the average tumor volume was 67.4 mm3, animals were divided into 4 groups: group 1 – controls (n = 5); group 2 – animals receiving paclitaxel (n = 5); group 3 – animals with XAV-939 (n = 5); group 4 – animals with combined paclitaxel+XAV-939 (n = 5). The control group received the carrier substance, and the test substances were administered at 10 mg/kg; the substances were administered intraperitoneally twice a week for 22 days. The tumor growth was assessed throughout the experiment by measuring its linear dimensions (length and width), and the volume and tumor growth index were calculated. The data were statistically processed using Microsoft Excel and STATISTICA 10. The Mann-Whitney nonparametric test was used to assess the differences between the control and experimental groups. Results: No statistically significant differences were observed in the indices of tumor growth between groups 2 (paclitaxel) and 1 (control), and groups 3 (XAV-939) and 1 (control). However, the difference was statistically significant between groups 4 (paclitaxel+XAV-939) and 1 (control). The tumor growth inhibition index was calculated at the end of the experiment. It was maximal in group 4 (paclitaxel+XAV-939) – 67.78%; in groups 2 (paclitaxel) and 3 (XAV-939), it was 21.39% and 30.33%, respectively. Conclusions: An orthotopic PDX model of ovarian cancer was generated, and the activity of XAV-939 towards the OC xenograft was studied; the greatest efficacy of the preparation was noted in combination with paclitaxel.