Universidade Federal do Rio Grande do Sul, Faculdade de Farmácia, Av. Ipiranga, 2752, 90610-000 Porto Alegre, RS, Brazil.
Universidade Federal do Rio Grande do Sul, Hospital de Clínicas de Porto Alegre e Faculdade de Medicina, Departamento de Patologia, Rua Ramiro Barcelos, 2400, 90035-002 Porto Alegre, RS, Brazil.
An Acad Bras Cienc. 2022 May 2;94(2):e20210670. doi: 10.1590/0001-3765202220210670. eCollection 2022.
Fatty acid synthase (FASN) is the rate-limiting enzyme for the de novo synthesis of fatty acids in the cytoplasm of tumour cells. Many tumour cells express high levels of FASN, and its expression is associated with a poorer prognosis. Cervical cancer is a major public health problem, representing the fourth most common cancer affecting women worldwide. To date, only a few in silico studies have correlated FASN expression with cervical cancer. This study aimed to investigate in vitro FASN expression in premalignant lesions and cervical cancer samples and the effects of a FASN inhibitor on cervical cancer cells. FASN expression was observed in all cervical cancer samples with increased expression at more advanced cervical cancer stages. The FASN inhibitor (orlistat) reduced the in vitro cell viability of cervical cancer cells (C-33A, ME-180, HeLa and SiHa) in a time-dependent manner and triggered apoptosis. FASN inhibitor also led to cell cycle arrest and autophagy. FASN may be a potential therapeutic target for cervical cancer, and medicinal chemists, pharmaceutical researchers and formulators should consider this finding in the development of new treatment approaches for this cancer type.
脂肪酸合酶（FASN）是肿瘤细胞细胞质中脂肪酸从头合成的限速酶。许多肿瘤细胞表达高水平的 FASN，其表达与预后不良相关。宫颈癌是一个主要的公共卫生问题，是全球女性中第四常见的癌症。迄今为止，只有少数计算机研究将 FASN 表达与宫颈癌相关联。本研究旨在研究宫颈前病变和宫颈癌样本中的体外 FASN 表达以及 FASN 抑制剂对宫颈癌细胞的影响。在所有宫颈癌样本中均观察到 FASN 表达，在更晚期的宫颈癌阶段表达增加。FASN 抑制剂（奥利司他）以时间依赖性方式降低宫颈癌细胞（C-33A、ME-180、HeLa 和 SiHa）的体外细胞活力，并触发细胞凋亡。FASN 抑制剂还导致细胞周期停滞和自噬。FASN 可能是宫颈癌的一个潜在治疗靶点，药物化学家、药物研究人员和制剂专家应在开发这种癌症类型的新治疗方法时考虑这一发现。
