Abstract 322P
Background
Gallbladder cancer (GBC) is a prevalent and aggressive malignancy of the biliary tract, with Indian cases contributing around 10% globally. Late-stage diagnosis and lack of targeted treatments contribute to its poor prognosis. Understanding molecular changes is crucial for early detection and treatment. Our recent findings demonstrated the deregulation of WNT signalling components in advanced GBC (Kumar et al,2020; Experimental Oncology). In this study, we explored the role of canonical WNT signalling pathway in Gall bladder cancer progression and metastasis.
Methods
The protein levels of key components (β-catenin, c-Myc, Cyclin D1) of the canonical WNT signalling pathway were evaluated in 30 Gall bladder cancer patients using Immunohistochemistry. For In vitro experiments, GBC cell lines OCUG1 and NOZ were used and XAV939 was used as a canonical WNT signalling pathway inhibitor. IC50 was determined via MTT assay, followed by analysis using western blotting, Immunofluorescence, migration, invasion, and colony formation assays in XAV939-treated cells.
Results
The results demonstrated that 60% of Gall bladder cancer patients have elevated protein levels of canonical WNT signalling components [β-catenin (64%), c-Myc (68%) and Cyclin D1(58%]. MTT assay showed that XAV939 is effective in reducing the viability of GBC cells (OCUG1 and NOZ). Western blot also showed a reduction in canonical WNT signalling pathway components: β-catenin, as well as downstream targets Cyclin D1 and c-Myc. XAV 939 also inhibited the migration, invasion or colony formation ability of Gall bladder cancer cells.
Conclusions
The study demonstrates that the canonical WNT signalling pathway is upregulated in Gall bladder cancer patients. XAV 939, a tankyrase inhibitor specifically targets WNT/ β-catenin signalling and cancer cell physiology in Gall bladder cancer cell lines.
Legal entity responsible for the study
The authors.
Funding
Indian council of medical research.
Disclosure
All authors have declared no conflicts of interest.