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Evaluation of radiolabeled acetate uptake as surrogate marker for fatty acid synthase expression and therapeutic effects of orlistat in human prostate carcinoma cells
https://repo.qst.go.jp/records/70818
https://repo.qst.go.jp/records/708180f87177c-a8f6-4c85-a934-ed6cadeb447e
Item type | 会議発表用資料 / Presentation(1) | |||||
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公開日 | 2012-07-04 | |||||
タイトル | ||||||
タイトル | Evaluation of radiolabeled acetate uptake as surrogate marker for fatty acid synthase expression and therapeutic effects of orlistat in human prostate carcinoma cells | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_c94f | |||||
資源タイプ | conference object | |||||
アクセス権 | ||||||
アクセス権 | metadata only access | |||||
アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
著者 |
Yoshii, Yukie
× Yoshii, Yukie× Furukawa, Takako× Oyama, Nobuyuki× Kiyono, Yasushi× Nishii, Ryuichi× Fujibayashi, Yasuhisa× Saga, Tsuneo× et.al× 吉井 幸恵× 古川 高子× 清野 泰× 西井 龍一× 藤林 康久× 佐賀 恒夫 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Objectives : Fatty acid synthase (FASN) expression is elevated in several human cancers and this over-expression is associated with poor prognosis. Orlistat, an inhibitor of FASN, is reported to show antitumor effects against FASN-expressing tumors. As variations in FASN expression in individual tumors have been observed, methods to evaluate FASN expression and predict therapeutic effects of orlistat are needed. Here, we examined whether uptake of radiolabeled acetate can act as a surrogate marker for FASN expression and as a predictor of therapeutic effects of orlistat using human prostate carcinoma cells showing various degrees of FASN expression. Methods : FASN expression, radiolabeled acetate uptake and therapeutic effect of orlistat were examined in vitro with human prostate cancer cells, including LNCaP, PC3, 22Rv1 and DU145. In acetate uptake study, cells were incubated in [1-14C]acetate-containing medium and radioactivity was measured. Cell viability after orlistat treatment for 48 h was determined. Tumor-bearing mice were also treated with orlistat (250 mg/kg/day) for 2 weeks to examine therapeutic outcome of orlistat in vivo. Results : LNCaP cells, which express high levels of FASN, showed high acetate uptake, while PC3, 22Rv1 and DU145, which express lower levels of FASN, showed relatively low acetate uptake. There was a significant positive correlation between acetate uptake and FASN expression. % cell viability after orlistat treatment showed significant negative correlations to acetate uptake and FASN expression, respectively. LNCaP tumors (high FASN) showed high acetate uptake and high sensitivity to orlistat treatment, while PC3 and DU145 tumors (low FASN) showed low acetate uptake and less sensitivity, in vivo. Conclusions : Our findings showed that uptake of radiolabeled acetate would be a potential surrogate marker for FASN expression in tumor cells, and is a predictor of the therapeutic effects of orlistat. \nJune 9-13, 2012– SNM Annual Meeting (Miami, Florida, USA) 2250 characters (approx. 300 words) Figure [1-14C]acetate uptake (A), FASN expression (B, C) and therapeutic effect of orlistat (D) in human prostate cancer cells, LNCaP, PC3, 22Rv1 and DU145. There was a significant positive correlation between [1-14C]acetate uptake and FASN expression (E). Percent cell viability after orlistat treatment showed significant negative correlations to [1-14C]acetate uptake (F) and FASN expression (G). Therapeutic effect of orlistat in vivo (H). |
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会議概要(会議名, 開催地, 会期, 主催者等) | ||||||
内容記述タイプ | Other | |||||
内容記述 | SNM 2012 Annual Meeting | |||||
発表年月日 | ||||||
日付 | 2012-06-13 | |||||
日付タイプ | Issued |