三氧化二砷联合5-氟尿嘧啶抗人大肠癌细胞的实验研究

 目的 探讨三氧化二砷（As2O3）与5-氟尿嘧啶（5-Fu）联合应用对人大肠癌细胞株CoLo-320的影响及其作用机制。方法 经不同浓度的As2O3和／或5-Fu处理CoLo-320细胞后，采用MTT法测定细胞的增生抑制效应；AO／EB荧光染色、DNA电泳、电镜、流式细胞术观察细胞凋亡、形态学和细胞周期变化；免疫组织化学法观察凋亡相关基因表达的变化。结果 与As2O3或5-Fu单药作用相比，As2O3与5-Fu联合应用可显著增强抑制CoLo-320细胞增生和诱导细胞凋亡作用，联合用药后细胞S期比例均较各单药使用时下降，癌细胞bcl-2基因表达明显下降，Bax和Fas基因表达显著增强。结论 As2O3与5-Fu联合应用具有显著协同抗大肠癌作用，其机制可能与增强诱导大肠癌细胞凋亡、细胞周期特异性药物与细胞周期调控剂联合增效以及调控凋亡相关基因的表达有关。

Study the anti-tumor effect and its mechanism of arsenic trioxide combined with fluorouracil on human large intestine carcinoma cell

Objective To study the anti-tumor effect of arsenic trioxide(As2O3) combined with fluorouracil(5-Fu) on the human large intestine carcinoma cell line CoLo-320 and explore its mechanism. Methods In vitro, human coloncarcinoma cell line CoLo-320 was treated by As2O3 and 5-Fu in various concentrations respectively alone or in combination, and then cell growth was assayed by MTT method, apoptosis, morphological and cell cycle changes were observed by acridine orange(AO)/ethidiumbromide(EB) fluorescent staining, DNA gel electrophoresis, electron microscopy detection and flow cytometry, and the expression of apoptosis-related genes were analyzed by immunohistochemical staining method. Results Compared with As2O3 or 5-Fu individual drug groups, As2O3 combined with 5-Fu obviously increased the inhibition rate and apoptosis rate of CoLo-320 cell, and the cell ratio of S phase was decreased with bcl-2 gene expression down-regulated, and Bax and Fas gene expression up-regulated. Conclusions Arsenic trioxide combined with 5-Fu may obviously increase the anti-large intestine carcinoma effect,and maybe its mechanism is increasing apoptosis-inducing effect which is regulated by several genes and enhancing the anti-tumor effect of cell cycle specific agent combined with cell cycle regulatory agent.