摘要
【目的】观察不同序贯的西妥昔单抗(cetuximab)与化疗药物联合对人肝癌细胞系HepG2和Bel-7402的增殖抑制作用,并分析其意义。【方法】浓度递增的cetuximab和表柔比星、奥沙利铂、泰素、伊立替康四种化疗药物分别按照不同给药序贯联合作用于HepG2和Bel-7402细胞,使用细胞计数试剂盒CCK-8检测不同给药序贯的药物对HepG2和Bel-7402细胞的增殖抑制作用,利用生物学软件Calcusyn计算不同给药序贯时cetuximab和化疗药物的半数抑制浓度(IC50)的变化,计算其作用的协同系数(CI)。【结果】Cetuximab和化疗药物联用对HepG2和Bel-7402细胞的增殖抑制作用受给药序贯影响:cetuximab先于化疗药物给药,两者的IC50较单用时降低,但是CI值均大于1,两者之间为拮抗效应;cetuximab后于化疗药物给药,两者的IC50较单用时降低更为明显,且CI值均小于1,两者之间具有较明显的协同效应。【结论】Cetuximab与化疗药物联用对肝癌细胞的增殖具有协同抑制作用,较佳的给药序贯是化疗药物先于cetuximab给药,能获得明显的协同效应,这有助于临床用药时降低药物剂量,减少毒副作用。
[Objective] To evaluate the inhibition effects of cetuximab on proliferation of HepG2 and Bel-7402 cells in different sequences of combination with either epirubicin, oxaliplatin, paclitaxel or irinotecan, explore the optimal treatment schedule of combination of cetuximab and cytotoxic drugs. [ Methods] Increasing concentrations of cetuximab（5-500 mg/mL）combined respectively with epirubicin（0.025-2.5 μmol/L）, oxaliplatin（0.5-50 μmol/L）, paclitaxel （0.001-0.1 μmol/L） or irinotecan（0.05-5 μmol/L） were administrated to HCC cell lines HepG2 and Bel-7402 with different sequences, the proliferation inhibition effects on HepG2 and Bel-7402 cells were detected with CCK-8 assay, the IC50 and CI of cetuximab and either of cytotoxic drug were calculated. [Results] The combination of a cytotoxic drug with cetuximab caused different antiproliferative effects on HepG2 and Bel-7402 cells depending on different treatment sequences. The respective IC50 of cetuximab and cytotoxic drugs decreased when cetuximab followed by chemotherapy, while the CI values were all 〉1, which indicated an antagonistic interaction. In contrast, when chemotherapy was followed by cetuximab, the respective IC50 of drugs decreased more remarkably and the CI values were all 〈1 ,which indicated a significant synergistic antiproliferative activity. [Conclusions ] The combination of cetuximab and cytotoxic drugs can increase the antiproliferative effects on HepG2 and Bel-7402 cells. The optimal treatment sequence is chemotherapy followed by cetuximab, it can obtain obvious synergistic activity and conduce to less doses and milder side effects in clinical application.
出处
《中山大学学报（医学科学版）》
CAS
CSCD
北大核心
2008年第5期556-561,共6页
Journal of Sun Yat-Sen University:Medical Sciences
基金
"十一五"国家科技支撑计划重大项目(2006BAI02A04)
关键词
肝肿瘤
西妥昔单抗
联合化疗
表皮生长因子受体
Liver neoplasm
cetuximab
combination chemotherapy
epidermal growth factor receptor
