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Fatty acid synthase is a key target to suppress tumor multiple functions: [1-11C]acetate PET as a predictor of the targeted therapy outcome
https://repo.qst.go.jp/records/64721
https://repo.qst.go.jp/records/64721f82aaa3a-41b1-4a08-b7eb-fac831eb6800
| Item type | 会議発表用資料 / Presentation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-09-12 | |||||
| タイトル | ||||||
| タイトル | Fatty acid synthase is a key target to suppress tumor multiple functions: [1-11C]acetate PET as a predictor of the targeted therapy outcome | |||||
| 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× Tsuji, Atsushi× Sogawa, Chizuru× Wakizaka, Hidekatsu× Yoshii, Hiroshi× Fujibayashi, Yasuhisa× Saga, Tsuneo× et.al× 吉井 幸恵× 古川 高子× 清野 泰× 西井 龍一× 辻 厚至× 曽川 千鶴× 脇坂 秀克× 吉井 裕× 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) is known to be over-expressed in several human cancers, e.g., prostate, breast, lung, and melanoma, and the over-expression is associated with poor prognosis (1). It is so far reported that orlistat, an inhibitor of FASN, shows antitumor effects (2). Hence, FASN is expected to be a promising therapeutic target for treatment of such cancers. However, large variations in FASN expression in individual tumors have been observed by pathological studies (3, 4), and therefore a method to predict therapeutic outcome of FASN-targeted therapy is needed to provide successful therapy for individual tumors. Also, how FASN inhibition affects tumor growth is still an open question. Here we examined whether [1-11C]acetate PET can evaluate FASN expression and predict outcome of FASN-targeted therapy, together with consequence of FASN inhibition in cancer therapy. Methods: Relationships between radiolabeled acetate uptake, FASN expression and therapeutic effect of orlistat were examined in vitro and in vivo with human prostate cancer cell lines including LNCaP, PC3, 22Rv1 and DU145. For in vitro studies, acetate uptake, FASN expression, and cell viability after orlistat treatment were determined. For in vivo studies, [1-11C]acetate PET, biodistribution study, and orlistat treatment (250 mg/kg/day for 2 weeks) were performed with tumor-bearing mice. To understand the mechanism how FASN inhibition affects tumor growth, FASN knockdown LNCaP cells were established by transduction of lentiviral particles carrying expression cassettes encoding single-hairpin RNA (shRNA) against FASN and the characteristics of the cells were examined in detail. Results: LNCaP cells, which express high levels of FASN, showed high acetate uptake, while PC3, 22Rv1 and DU145, which express low levels of FASN, showed relatively low acetate uptake. There was a significant positive correlation between acetate uptake and FASN expression. Percentage of cell viability after orlistat treatment showed significant negative correlations to acetate uptake and FASN expression, respectively. From in vivo studies, 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 low sensitivity to orlistat treatment. Interestingly, we found that knockdown of FASN by shRNA suppressed cell proliferation, cell adhesion, migration and invasion with down-regulation of genes related to these functions. Conclusions: Our findings showed that FASN is a key target to suppress multiple steps related to tumor progression and [1-11C]acetate PET is a powerful tool to accomplish individualized FASN-targeted therapy by non-invasively predicting the therapeutic outcome. | |||||
| 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 | 2012 World Molecular Imaging Congress | |||||
| 発表年月日 | ||||||
| 日付 | 2012-09-08 | |||||
| 日付タイプ | Issued | |||||
