Sokolowska Ewa, Presler Malgorzata, Goyke Elzbieta, Milczarek Ryszard, Swierczynski Julian, Sledzinski Tomasz
Department of Pharmaceutical Biochemistry, Medical University of Gdansk, Gdansk, Poland.
Department of Biochemistry, Medical University of Gdansk, Gdansk, Poland.
Anticancer Res. 2017 Nov;37(11):6321-6327. doi: 10.21873/anticanres.12083.
BACKGROUND/AIM: Pancreatic cancer is a disease with very poor prognosis, and none of currently available pharmacotherapies have proven to be efficient in this indication. The aim of this study was to analyze the expression of fatty acid synthase (FASN) gene as a potential therapeutic target in proliferating human pancreatic cancer cells (PANC-1), and verify if orlistat, originally developed as an anti-obesity drug, inhibits PANC-1 proliferation.
The effects of orlistat on gene expression, lipogenesis, proliferation and apoptosis was studied in PANC-1 cell culture.
Expression of FASN increased during proliferation of PANC-1. Inhibition of FASN by orlistat resulted in a significant reduction of PANC-1 proliferation and enhanced apoptosis of these cells.
This study showed, to our knowledge for the first time, that orlistat exhibits significant antitumor activity against PANC-1 cells. This implies that orlistat analogs with good oral bioavailability may find application in pharmacotherapy of pancreatic cancer.
背景/目的:胰腺癌是一种预后很差的疾病,目前可用的药物治疗在该适应症中均未被证明有效。本研究的目的是分析脂肪酸合酶(FASN)基因在人胰腺癌细胞(PANC-1)增殖中的表达作为潜在治疗靶点,并验证最初作为抗肥胖药物开发的奥利司他是否抑制PANC-1增殖。
在PANC-1细胞培养中研究了奥利司他对基因表达、脂肪生成、增殖和凋亡的影响。
在PANC-1增殖过程中FASN表达增加。奥利司他抑制FASN导致PANC-1增殖显著降低,并增强了这些细胞的凋亡。
据我们所知,本研究首次表明奥利司他对PANC-1细胞具有显著的抗肿瘤活性。这意味着具有良好口服生物利用度的奥利司他类似物可能在胰腺癌的药物治疗中得到应用。