饶子超¹   郭鹏¹   刘东²   雷晓林¹  陈兆聪²  张阿丽²  张春燕²

(1.武汉大学药学院  武汉 430072； 2.华中科技大学同济医学院附属同济医院)

摘 要 目的：体外观察紫杉醇及抗HER2单克隆抗体对人卵巢癌细胞株A2780增殖的抑制作用及两者联合应用时的抑制率及相互作用。方法：采用MTT法测定两者单用或合用对A2780的增殖抑制率, 利用中效原理判定两药合用的效果，用流式细胞仪观察凋亡及细胞周期的变化。结果：两种药单独应用时随着药物剂量增加,其效应也增加,紫杉醇的中效浓度为6.98nmol·L^-1, 抗HER2单克隆抗体的中效浓度为8.69μg·ml^-1;两药合用时它们的中效浓度为 2.92 nmol·L^-1+0.49μg·ml^-1。大剂量(紫杉醇>13.02 nmol·L^-1，抗HER2单抗>2.17μg·ml^-1)合用时是拮抗作用(CI>1), 小剂量(紫杉醇<13.02 nmol·L^-1，抗HER2单抗<2.17μg·ml^-1)合用时是协同作用(CI<1)。结论：紫杉醇联合抗HER2单克隆抗体对人卵巢癌细胞株A2780的生长有抑制作用,它们合用时大剂量是拮抗, 而小剂量则为协同作用。

关键词  药物联合应用；中效原理；卵巢癌；紫杉醇；抗HER2单抗

United Effects of Taxol and Anti-HER2 Mono-Antibody (mAb) on Human Ovarian Cancer Cell Strain A2780

Rao Zichao¹， Guo Peng¹， Liu Dong²， Lei Xiaolin¹， Chen Zhaocong²，Zhang A’li², Zhang Chunyan² (1.College of Pharmacy, Wuhan University, Wuhan, 430072, P.R.China; 2.Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology)

ABSTRACT Objective: To observe the inhibiting effects of TAX and anti HER2 mAb on human ovarian cancer cell strain A2780 and the inhibiting rate and interaction when the two drugs were used together. Methods: The inhibition of Taxol and anti HER2 mAb on A2780 cells used together or separately was measured by MTT assay. The interaction effect of two drugs was analyzed with median-effect principle. The changes of cell period and the apoptosis were observed by using flow cytometer (FCM). Results: The effects of the individual drugs were enhanced as drug dosage increased. The median concentration of Taxol was 6.98 nmol·L^-1 and that of anti-HER2 mAb was 8.69μg·ml^-1 , The median concentration of combination of two drugs was 2.92 nmol·L^-1+0.49μg·ml^-1. The interaction of two drugs was antagonistic at higher concentration(Concentration of Taxol>13.02 nmol·L^-1, Concentration of anti-HER2 mAb>2.17μg·ml^-1)(CI＞1)and synergistic at lower concentration(Concentration of Taxol<13.02 nmol·L^-1, Concentration of anti-HER2 mAb<2.177μg·ml^-1)(CI＜1). Conclusion: The united effect of the Taxol and anti-HER2 mAb on A2780 cells is antagonistic at higher concentration and synergistic at lower concentration.

KEY WORDS Drug combination; Median-effect principle; Ovarian cancer; Taxol; anti HER2 mAb