Evaluation of Fgf19 Role in Cholangiocarcinoma and Application the Newest Vitamin D Analog, Mart-11, to Treat Cholangiocarcinoma

Cholangiocarcinoma (CCA) is a devastating disease with increasing incidence in Taiwan recently. Radical surgery is the cornerstone of treatment for CCA patients. However, the late onset of symptoms usually leads to the unfeasibility of surgery. Adding the resistance of CCA to traditional chemotherapies and radiotherapies, advanced CCA patients have a poor prognosis. Thus, to develop new therapeutic targets and regimens against CCA should be prioritized. FGF 19( fibroblast growth factor 19) is deemed as on new oncogene in prostate, breast, oral squamous, liver, and lung cancer and high expression of FGF 19 has been linked with poor prognosis in patients with these cancers. However, the details concerning the regulatory mechanisms and downstream genes of FGF 19 in cancer cells have not been well studied yet and studies about functions of FGF 19 in CCA are very limited.. Our preliminary data show FGF 19 expresses in at least 8 kinds of CCA cells. Knockdown of FGF 19 could decrease CCA cell growth, migration and invasion. CCA cells with FGF 19 overexpression would increase CCA cell growth and metastasis. Furthermore, FGF 19 overexpression could enhance CCA cell growth and metastasis in xenograft nude mice and zebrafish models. In addition, we showed that 1α25(OH)2D3 and its analog MART-10 could effectively repress CCA cell growth in vitro and in vivo and this data has been published in the SCI paper, indicating 1α25(OH)2D3 analog has the potential to treat CCA. In this three year proposal, we aim to investigate the role of FGF 19 in CCA, including FGF 19 effects on CCA cell growth ad metastasis in vitro and in vivo through xenograft animal models in nude mice and zebrafishes. The detailed mechanisms of how FGF 19 works and is regulated will also been investigated. We will further investigate the effect of the newest 1α25(OH)2D3 analog, MART-11, on CCA and FGF 19 expression. We hope through this work, we can provide more new targets and new treatment regimens for CCA treatment to prolong CCA patients survival.

Project ID:PC10901-1664
External Project ID:MOST108-2314-B182-067-MY3