Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan.
Prostate Cancer Prostatic Dis. 2012 Sep;15(3):260-4. doi: 10.1038/pcan.2012.15.
Fatty acid synthase (FASN) is highly upregulated in human prostate carcinomas. Inhibition of FASN could arrest cell cycle and trigger apoptosis rapidly, implying the reliance of cancer cell survival on FASN. However, little is known about the effect of C75, a FASN inhibitor, and siFASN (that is, small interfering RNA targeted at FASN) on prostate cancer in living subjects.
We used C75 and siFASN to mediate the endogenous fatty acid metabolism in LNCaP human prostate cancer cells stably expressing herpes simplex virus type 1 thymidine kinase (HSV1-tk) and luciferase (luc) reporter genes, and assessed the effect of FASN blockade with different schedules of administration on tumor growth using noninvasive molecular imaging.
FASN blockade exhibited the proliferative inhibition and induced G1-phase cell cycle arrest of LNCaP cells. For in vivo studies, the tumor growth inhibition by C75 (total 120 mgkg(-1); 30 mgkg(-1) once a week or 15 mgkg(-1) twice a week for 4 weeks) and siFASN (1.4 mgkg(-1) every alternate day up to 16 days) treatments were 80% and 70%, respectively, compared with that of the control.
The results suggest that C75 may be superior to siFASN in anticancer effect on prostate cancer.
脂肪酸合酶（FASN）在人前列腺癌中高度上调。FASN 的抑制作用可迅速阻滞细胞周期并引发细胞凋亡，这意味着癌细胞的存活依赖于 FASN。然而，对于 FASN 抑制剂 C75 和靶向 FASN 的小干扰 RNA（siFASN）在活体对象中对前列腺癌的影响，我们知之甚少。
我们使用 C75 和 siFASN 来调节稳定表达单纯疱疹病毒 1 胸苷激酶（HSV1-tk）和荧光素酶（luc）报告基因的 LNCaP 人前列腺癌细胞中的内源性脂肪酸代谢，并使用非侵入性分子成像来评估不同给药方案的 FASN 阻断对肿瘤生长的影响。
FASN 阻断显示出对 LNCaP 细胞的增殖抑制和诱导 G1 期细胞周期阻滞。在体内研究中，C75（总剂量 120mgkg(-1)；30mgkg(-1)每周一次或 15mgkg(-1)每周两次共 4 周）和 siFASN（1.4mgkg(-1)每隔一天直至 16 天）处理的肿瘤生长抑制分别为 80%和 70%，与对照组相比。
结果表明，C75 在抗前列腺癌方面可能优于 siFASN。
