Cholangiocarcinoma (CC) is a devastating cancer, which affects any area of the bile ducts. The new cases of CC have increased in the Western countries. Besides, CC is also an endemic in several Southeast Asia countries such as Thailand and Myanmar. CC is notoriously challenging to diagnose and treat. Currently, only surgical resection is associated with improvement of 5-year survival rate. However, distant metastases, extensive regional lymph node metastasis and vascular encasement or invasion preclude surgical resection. Our previous report showed that the p38δ gene expression was up-regulated in CC tumor sample as well as in CC cell lines. In this study, we further found that inhibition of p38δ by BIRD0796, a p38 δ inhibitor impaired migration ability in CC cell line EGI-1 in vitro (p = 0.006232). The result was further confirmed with p38δ siRNA knowdown (p = 0.0005) and plasmid over-expression experiments (p = 0.003). Interestingly, BIRD0796 did not exhibit similar inhibition effect on migration in TGB cells (p > 0.05). Analysis of p53 gene sequences revealed that there is a frame shift mutation (c.525 526insGCGC) in TGB cells but not any of functional mutation in EGI-1 cells. It indicates that the migration inhibition effect of BIRD0796 in CC metastasis may dependent on p53. Our results suggest that BIRD0796 may be a potential chemotherapeutic compound for CC.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 425.