脂肪酸合酶抑制剂 TVB-3166 对口腔鳞状细胞癌细胞系的抗癌特性。
Anticancer properties of the fatty acid synthase inhibitor TVB-3166 on oral squamous cell carcinoma cell lines.
机构信息
Department of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, Sao Paulo, Brazil.
Department of Oral Diagnosis, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, Sao Paulo, Brazil; Department of Morphology, School of Dentistry of Piracicaba, State University of Campinas (UNICAMP), Piracicaba, Sao Paulo, Brazil.
出版信息
Arch Oral Biol. 2020 May;113:104707. doi: 10.1016/j.archoralbio.2020.104707. Epub 2020 Mar 10.
OBJECTIVE
Fatty acid synthase (FASN) is overexpressed in several human cancers, including oral squamous cell carcinoma (OSCC). TVB-3166 is a recently described FASN inhibitor with antitumor effects and potential clinical relevance. The objective of this study was to evaluate the effects of TVB-3166 on OSCC cell lines.
MATERIALS AND METHODS
The OSCC cell line SCC-9 modified to express ZsGreen (ZsG) (SCC-9 ZsG) and its in vivo selected metastatic derivative LN-1A were used to evaluate anticancer properties of TVB-3166. Cell viability was determined using MTT assays and proliferation determined by cell counting in a Neubauer chamber. Cell death and cell cycle progression were analyzed by Annexin V-PE/7-ADD-PerCP labeling and PI staining, respectively. Cell migration was assayed by scratch assays and cell adhesion using myogel. Production of FASN, p-AKT, CPT1-α, and epithelial-mesenchymal transition (EMT) markers were examined by Western blotting.
RESULTS
TVB-3166 significantly reduced cell viability and proliferation, promoted cell cycle arrest and apoptosis, and increased adhesion to myogel in both OSCC cell lines. Finally, the drug reduced SCC-9 ZsG migration.
CONCLUSION
Our results demonstrated that TVB-3166 has anticancer effects on both SCC-9 ZsG and its metastatic version LN-1A, which are worthy of investigation in preclinical models for OSCC.
目的
脂肪酸合酶（FASN）在多种人类癌症中过表达，包括口腔鳞状细胞癌（OSCC）。TVB-3166 是一种最近描述的 FASN 抑制剂，具有抗肿瘤作用和潜在的临床相关性。本研究的目的是评估 TVB-3166 对 OSCC 细胞系的影响。
材料和方法
将表达 ZsGreen（ZsG）的 OSCC 细胞系 SCC-9 进行修饰（SCC-9 ZsG）及其体内选择的转移性衍生系 LN-1A 用于评估 TVB-3166 的抗癌特性。使用 MTT 测定法测定细胞活力，并通过 Neubauer 室中的细胞计数测定增殖。通过 Annexin V-PE/7-ADD-PerCP 标记和 PI 染色分别分析细胞死亡和细胞周期进程。通过划痕实验和使用 myogel 测定细胞粘附来测定细胞迁移。通过 Western 印迹检查 FASN、p-AKT、CPT1-α 和上皮间质转化（EMT）标志物的产生。
结果
TVB-3166 显著降低了两种 OSCC 细胞系的细胞活力和增殖，促进了细胞周期停滞和凋亡，并增加了对 myogel 的粘附。最后，该药物减少了 SCC-9 ZsG 的迁移。
结论
我们的结果表明，TVB-3166 对 SCC-9 ZsG 及其转移性版本 LN-1A 均具有抗癌作用，值得在 OSCC 的临床前模型中进行研究。
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