MET‑RON dual inhibitor, BMS‑777607, suppresses cholangiocarcinoma cell growth, and MET‑RON upregulation indicates worse prognosis for intra‑hepatic cholangiocarcinoma patients

Abstract

Intra‑hepatic cholangiocarcinoma (CCA) is an aggressive cancer with few effective therapeutic options. MET and RON have been found to be increased in a variety of tumors and to be associated with tumor progression and acquired resistance to therapy. The present study evaluated the efficacy of a MET‑RON dual inhibitor (BMS‑777607) for treating CCA and analyzed the prognostic significance of MET‑RON upregulation. We treated CCA cell lines and rats with CCA with BMS‑777607 to determine its effects on tumor growth and measured the MET‑RON protein expression in samples obtained from 96 patients with CCA who previously underwent hepatectomies. A clonogenic assay revealed that BMS‑777607 inhibited the growth of HuCCT1 and KKU‑100 human CCA cells. It also decreased tumor growth in CCA rats. MET‑RON upregulation independently predicted poor survival for CCA patients who previously underwent hepatectomies. In conclusion, MET‑RON upregulation is a poor prognostic factor in CCA patients receiving hepatectomies and may be targeted using BMS‑77760.