伊立替康、奥沙利铂及氟尿嘧啶对人大肠癌LoVo细胞株作用的实验研究

Study on anti-proliferation effect of irinotecan,oxaliplatin and fluorouracil on colorectal carcinoma cell line LoVo in vitro

目的:研究国产盐酸伊立替康(CPT-11)、奥沙利铂(L-OHP)及氟尿嘧啶(5-FU)对人大肠癌细胞株LoVo的生长抑制作用。方法:采用MTT法观察上述药物单药应用、两药及三药同时或序贯联合应用对大肠癌LoVo细胞生长的影响,评价药物联合应用的效果。结果:单药应用、两药联合及三药联合应用均对大肠癌LoVo细胞有显著的抑制作用(P<0.05);两药联合应用均优于各自单药的抑制效果,CPT-11联合L-OHP弱于CPT-11或L-OHP与5-FU联合的抑制效果(P<0.05),由L-OHP到CPT-11小剂量序贯联合具有明显的协同作用;三药联合应用的抑制效果显著优于两药联合(P<0.05),由5-FU+L-OHP到5-FU+CPT-11的序贯联合应用与三药同步联合应用无显著性差异(P>0.05),但由5-FU+CPT-11到5-FU+L-OHP序贯应用时明显低于三药同步应用的效果(P<0.05),且三药全量及半量联合应用效果差异无显著性(P>0.05)。结论:由5-FU+L-OHP到5-FU+CPT-11的小剂量序贯联合应用具有高效协同抑制大肠癌细胞株LoVo的作用,可为临床难治性和复发性大肠癌患者的化疗及小剂量序贯化疗提供参考。

Objective： To study the growth-inhibition effect of irinotecan （ CPT-11 ）, oxaliplatin （L-OHP） and fluorouracil （ 5-FU） on human colorectal carcinoma cell line LoVo. Methods：The growth-inhibition effects of single drug, concurrent and sequential combination of two or three drugs on human colorectal carcinoma cell line LoVo were observed by MTT assay, and the synergistic effect of these drugs was evaluated. Results： Single, two and three drugs combinations all showed the anti-proliferation effects on LoVo cell line（P 〈0. 05）. The inhibitory rates of any two drugs were significantly higher than those in single drug group. The growth-inhibition effect of CPT-11 combined with L-OHP was lower than that of CPT-11 or L-OHP combined with 5-Fu（ P 〈 0. 05 ）, and synergetic effect was observed in the L-OHP to CPT-11 sequence. The growth-inhibition effect of the three drugs combination was significantly enhanced compared with regiment of two drugs combination chemotherapy. The 5-FU ＋ L-OHP to 5-FU ＋ CPT-11 schedule reached similar cell growth inhibitory rate compared with simultaneous combination of three drugs on human colorectal carcinoma cell line LoVo （P 〉 0. 05）, while the growth-inhibition effect of sequential combination of three drugs in the 5-FU ＋ CPT-11 to 5-FU ＋ L-OHP sequence was lower than simultaneous combination of the three drugs（P 〈 0. 05）. Furthermore, whole-dose and half-dose combination of 3 drugs reached similar cell growth inhibitory rate （P 〉 0. 05 ）. Conclnsions：The regiment of sequential combination of three drugs in the 5-FU ＋ L-OHP to 5-FU ＋ CPT-11 sequence with lower dose can synergistically inhibit the proliferation of human colorectal carcinoma cell line LoVo, which provided reference for the chemotherapy of refractory and recurrent colorectal carcinoma patients and sequential combination with low dose use of drugs in chemotherapy.