Xing Ying, Wang Zhi Hong, Ma Dong Hong, Han Ying
J Dig Dis. 2014 May;15(5):246-59. doi: 10.1111/1751-2980.12131.
This study aimed to investigate the effects of FTY720 on inducing cell growth inhibition and enhancing the cytotoxicity of anti-cancer drugs in the human colon cancer cell line HCT-8 and its multidrug-resistant cell line HCT-8/5-fluorouracil (HCT-8/5-Fu).
Cell viability and apoptosis after being treated with FTY720 alone or in combination with doxorubicin (DOX) and etoposide (VP16) were tested in HCT-8 and HCT-8/5-Fu cells. The changes in P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) were determined at the mRNA and functional levels.
FTY720 showed anti-proliferative activity against cancer cells in a dose-dependent and time-dependent manner and could enhance the cytotoxicity of DOX and VP16 in both HCT-8 and HCT-8/5-Fu cell lines. In addition, treatment with FTY720 resulted in the promotion of VP16-induced cell apoptosis and an increased accumulation of intracellular DOX and two specific fluorescent substrates of P-gp and MRP1 through the inhibition of efflux and the suppression of gene expression.
FTY720 exerts its chemosensitization effect in HCT-8 and HCT-8/5-Fu cell lines by promoting cell apoptosis and inhibiting P-gp and MRP1, which could be applied as a potential co-adjuvant therapeutic modality.
本研究旨在探讨FTY720对人结肠癌细胞系HCT - 8及其多药耐药细胞系HCT - 8/5 - 氟尿嘧啶（HCT - 8/5 - Fu）诱导细胞生长抑制及增强抗癌药物细胞毒性的作用。
在HCT - 8和HCT - 8/5 - Fu细胞中检测单独使用FTY720或与阿霉素（DOX）和依托泊苷（VP16）联合使用后细胞的活力和凋亡情况。在mRNA和功能水平上测定P - 糖蛋白（P - gp）和多药耐药蛋白1（MRP1）的变化。
FTY720对癌细胞具有剂量依赖性和时间依赖性的抗增殖活性，并且能增强DOX和VP16对HCT - 8和HCT - 8/5 - Fu细胞系的细胞毒性。此外，FTY720处理导致VP16诱导的细胞凋亡增加，以及通过抑制流出和抑制基因表达使细胞内DOX以及P - gp和MRP1的两种特异性荧光底物积累增加。
FTY720通过促进细胞凋亡和抑制P - gp及MRP1在HCT - 8和HCT - 8/5 - Fu细胞系中发挥化学增敏作用，可作为一种潜在的辅助治疗方式应用。
