2022-RA-1582-ESGO Inhibition of the Wnt/β-Catenin pathway with DKK3 protein – a new viral therapy for treatment of ovarian cancer?. (20th October 2022)

• Record Type: Journal Article
• Authors: Naskretski, Adam; Robinson, Andrew; Meniel, Valerie; Jones, Sadie; Phesse, Toby; Parker, Alan
• Is Part Of: International journal of gynecological cancer. Volume 32(2022)Supplement 2
• Page Start: A419
• Page End: A419
• Publication Date: 2022-10-20
• Subjects: Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2022-ESGO.899
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Introduction/Background: Wnt/β-Catenin signalling pathway plays an important role in many cellular processes, including cell proliferation. Abnormal functioning of the pathway has been demonstrated in ovarian cancer and therefore could be the focus for novel treatments, including viral therapies. In this study, we examined the effects of Wnt/β-Catenin pathway inhibition in ovarian cancer by infecting ovarian cancer cells with modified adenovirus 5 (Ad5) expressing Dickkopf-3 (DKK3) protein, a known Wnt/β-Catenin pathway inhibitor Methodology: DKK3 expression in the virus was confirmed by quantitative PCR test against DKK3 and other Wnt target genes and Western Blot. Once confirmed, 10k epithelial ovarian cancer cells (SKOV3 cell line) were infected with the modified virus at 1k, 2.5k, 5k and 10k virus particles per cell for CellTiter Glo (CTG) assay with results analysed at 24, 48 and 72hrs post infection. In Colony Forming Assay, 300 SKOV3 cells were infected at the same virus particles per cell ratios and analysed after 14 days. The same assays were performed with doxorubicin and Ad5RAD as positive and negative controls respectively. Results: CTG assay showed reduced cell viability and proliferation of cancer cells for the first 48hrs post infection. In the colony forming assay, ovarian cancer cells were able to form multiple colonies of more than 50 cells 2 weeks after viral suppression of the Wnt/β-Catenin pathway, indicating the inhibition may not have long standing effects on cancer cells' ability to grow and multiply. Conclusion: Our results indicate infecting cancer cells with Ad5 expressing DKK3 successfully inhibits the Wnt/β-Catenin pathway and leads to short-term reduction in cell proliferation. Further studies are needed to establish any long-term effects and potential translation into clinical practice.