Open AccessCombination with third‐generation bisphosphonate ( YM 529) and interferon‐alpha can inhibit the progression of established bone renal cell carcinoma
Author(s) -
Kurabayashi Atsushi,
Inoue Keiji,
Fukuhara Hideo,
Karashima Takashi,
Fukata Satoshi,
Kawada Chiaki,
Shuin Taro,
Furihata Mutsuo
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12711
Subject(s) - osteoclast , bisphosphonate , cancer research , in vivo , bone resorption , cell growth , apoptosis , chemistry , renal cell carcinoma , alpha interferon , cell culture , in vitro , biology , interferon , pathology , endocrinology , medicine , immunology , biochemistry , osteoporosis , genetics , microbiology and biotechnology
The aim of this study was to investigate whether the third‐generation nitrogen‐containing bisphosphonate ( YM 529) can inhibit the progression of established bone renal cell carcinoma ( RCC ) and to elucidate its mechanism. Antiproliferative effect and apoptosis induction of RCC cells and mouse osteoclasts by YM 529 and/or interferon‐alpha ( IFN ‐α) were evaluated in vitro using cell counting and in vivo using soft X‐ray, the TUNEL method and tartrate‐resistant acid phosphatase stain. For the in vivo study, male athymic BALB / cA Jc1‐nu nude mice bearing human RCC cell line RBM 1‐ IT 4 cells were treated with YM 529 and/or IFN ‐α. The biological activity of osteoclasts was evaluated using the pit formation assay. The antiangiogenetic effect by YM 529 and/or IFN ‐α was analyzed using micro‐vessel density and in situ mRNA hybridization. Osteoclast number in bone tumors was decreased in YM 529‐treated mouse. YM 529 also inhibited osteoclast activity and proliferation in vitro , whereas basic fibroblast growth factor expressions and micro‐vessel density within tumors were inhibited by IFN ‐α. Neither YM 529 nor IFN ‐α alone significantly inhibited the growth of established bone metastatic tumors. Combined treatment with YM 529 and IFN ‐α may be beneficial in patients with human RCC bone metastasis. Their effects are mediated by osteoclast recruitment inhibition and inactivation by YM 529 and antiangiogenesis by IFN ‐α.