Aoe K, Kiura K, Ueoka H, Tabata M, Matsumura T, Chikamori M, Matsushita A, Kohara H, Harada M
Second Department of Medicine, Okayama University Medical School, Japan.
Anticancer Res. 1999 Jan-Feb;19(1A):291-9.
Docetaxel shows substantial activity against lung cancer. To find the optimal drug combination for docetaxel, we evaluated the effects of cisplatin, etoposide, mitomycin C, irinotecan, vindesine, and vinorelbine using three human lung cancer cell lines, ABC-1, EBC-1, and SBC-3. Drug cytotoxicity was determined by MTT assay. Tumor cells were incubated for 96 hours in the presence of docetaxel and each of the test drugs stated above. The combined drug interaction was evaluated by median-effect plot analysis and improved IC50-isobologram analysis. Both methods showed strong antagonism (subadditive or protective effect) between docetaxel and etoposide when tested on ABC-1 and EBC-1 cells. Docetaxel and cisplatin displayed additive effects on all cell lines tested, when evaluated by improved IC50-isobologram analysis. The combination of docetaxel and vinorelbine exerted synergistic effect on the growth inhibition of SBC-3 cells, which showed a wide range of fractional cytotoxicity when analyzed by median-effect plot and supraadditive when analyzed by improved IC50-isobologram. These observations suggest a possibility that docetaxel can be used in combination with vinorelbine or cisplatin in the treatment of lung cancer.
多西他赛对肺癌显示出显著活性。为了找到多西他赛的最佳联合用药方案,我们使用三种人肺癌细胞系ABC - 1、EBC - 1和SBC - 3评估了顺铂、依托泊苷、丝裂霉素C、伊立替康、长春地辛和长春瑞滨的效果。通过MTT法测定药物细胞毒性。肿瘤细胞在多西他赛及上述每种受试药物存在的情况下孵育96小时。通过中位效应图分析和改进的IC50等效线图分析评估联合药物相互作用。在ABC - 1和EBC - 1细胞上进行测试时,两种方法均显示多西他赛和依托泊苷之间存在强拮抗作用(亚相加或保护作用)。通过改进的IC50等效线图分析评估时,多西他赛和顺铂在所有测试的细胞系上均显示相加作用。多西他赛和长春瑞滨的联合用药对SBC - 3细胞的生长抑制发挥协同作用,通过中位效应图分析显示出广泛的部分细胞毒性,通过改进的IC50等效线图分析显示超相加作用。这些观察结果提示多西他赛有可能与长春瑞滨或顺铂联合用于肺癌治疗。