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Exploring the efficacy of XAV939 and LF3 in targeting β-catenin signalling in gallbladder cancer cell lines
Akanksha Kashyap1, Sheikh Mohammad Umar1, Arundhathi J R Dev1
1Department of Medical Oncology Lab, DR BRA IRCH, All India Institute of Medical Sciences (AIIMS), New Delhi, 110029, India.
Purpose:
Gallbladder cancer (GBC) is a common biliary malignancy in India, with poor prognosis and disappointing outcomes despite radical surgery, including high recurrence rates and low 5-year survival. This underscores the urgent need for more effective treatments. Recent research highlights the WNT/β-catenin signalling pathway upregulation in GBC, suggesting it as a promising therapeutic target.
Methods:
In this study, we evaluated the effectiveness of two β-catenin inhibitors, XAV939 and LF3, in GBC cell lines OCUG1 and NOZ. Using the MTT assay, we determined the IC50 values of both inhibitors, and Western blotting was employed to assess β-catenin expression and its downstream transcriptional targets. We also examined changes in cell migration, invasion, and colony formation, and assessed nuclear β-catenin inhibition via immunofluorescence.
Results:
The IC50 values for XAV939 were 25µM for OCUG1 and 50µM for NOZ cells, while LF3 had IC50 values of 100µM for OCUG1 and 50µM for NOZ cells. LF3 treatment reduced β-catenin and its downstream targets: c-Myc, and cyclin D1 expression at sub-optimal doses, showing superior efficacy compared to XAV939.
Conclusions:
Compared to XAV939, LF3 more effectively inhibits nuclear β-catenin, might resulting in lower off-target toxicity and making it a favorable clinical candidate for targeting GBCs.
