Axitinib (AG-013736), an oral specific VEGFR TKI, shows potential therapeutic utility against cholangiocarcinoma

Hiroyuki Takahashi, Hidenori Ojima, Hiroko Shimizu, Junji Furuse, Hiroyuki Furukawa, Tatsuhiro Shibata

研究成果: Article査読

19 被引用数 (Scopus)

抄録

Objective: Cholangiocarcinoma is a refractory cancer whose incidence has been increasing worldwide in recent years. Neoangiogenesis plays an important role in the growth of various solid cancers, including cholangiocarcinoma. Vascular endothelial growth factor plays an important role in tumor-induced angiogenesis and its expression is associated with the progression and prognosis of cholangiocarcinoma. This study examined whether axitinib (AG-013736, INLYTA®), a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3, could be a potentially useful therapeutic agent for cholangiocarcinoma. Methods: We performed expression profiling of angiogenesis-related molecules in eight cholangiocarcinoma cell lines and found that three of them showed high vascular endothelial growth factor expression. Among them, we examined the in vivo anti-tumor effect of axitinib on NCC-BD1 (a gemcitabine-sensitive extra-hepatic cholangiocarcinoma cell line) and TKKK (a gemcitabine-resistant intra-hepatic cholangiocarcinoma cell line) using subcutaneous xenograft models. Results: Oral administration of axitinib significantly inhibited the growth of TKKK xenografts at a dose of 6 mg kg-1 day-1 (P,0.05), and the growth of NCC-BD1 xenografts at 30 mg kg-1 day-1 (P,0.05). Treated tumors showed a significant decrease of microvessel density and the tumor cell proliferation index and a mild but significant increase of the apoptotic index in comparison with untreated tumors. Conclusions: Our results suggest that axitinib should be a promising therapy for vascular endothelial growth factor-expressing cholangiocarcinoma, irrespective of tumor origin and gemcitabine sensitivity.

本文言語English
論文番号hyu045
ページ(範囲)570-578
ページ数9
ジャーナルJapanese journal of clinical oncology
44
6
DOI
出版ステータスPublished - 2014 6
外部発表はい

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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