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[摘要]
目的 研究去氢骆驼蓬碱衍生物B-9-3与5种不同传统抗肿瘤药联用的体外抑瘤作用。方法 经B-9-3(0.78~200.00 μg/mL)与紫杉醇、长春新碱、5-氟尿嘧啶、顺铂和表柔比星(0.78~200.00 μg/mL)单独及联合作用于肺癌细胞LLC、结肠癌细胞HT-29、肝癌细胞HepG2和乳腺癌MCF-7 48 h后,采用MTT法检测肿瘤细胞存活率,并按照WEBB法计算联合用药协同系数(Q);进一步通过PI/Hoechst 33342双荧光染色和细胞划痕实验研究B-9-3(0.78、25.00和200.00 μg/mL)作用于LLC细胞24 h后对瘤细胞活性、迁移的影响。结果 与B-9-3单独用药比较,同浓度B-9-3与长春新碱和紫杉醇联合用药,能够显著降低MCF-7和HT-29细胞的存活率,Q均低于0.3(Q < 1为协同)。荧光染色和细胞划痕实验结果表明,与溶剂对照组比较,B-9-3(25和200 μg/mL)组细胞凋亡明显增多、划痕修复率显著降低(P < 0.01)。结论 B-9-3显著抑制LLC细胞迁移能力并提高细胞凋亡率,与不同抗肿瘤药物联合具有协同作用。
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[Abstract]
Objective To investigate the inhibitory effect of B-9-3 combined with five anti-cancer drugs on different tumor cells. Methods LLC, HT-29, HepG2, and MCF-7 cells were treated with B-9-3 (0.78~200.00 μg/mL) and Vincristine, Taxol, 5-fluorouracil, Cisplatin and Epirubicin in single-group or in combination for 48 h separately. The inhibitory effect on growth of tumor cells was determined by MTT assay, and the combination index (Q) was calculated according to WEBB method. In addition, the apoptosis rate and migration of LLC cells after 24 h treatment of B-9-3 in different consetration (0.78、25.00和200.00μg/mL) were determined by PI/Hoechst33342 fluorescence staining and cell scratch test. Results Compared with B-9-3 alone group, B-9-3 in the same concentration combined with vincristine and paclitaxel reduced the survival rate of MCF-7 and HT-29 cells significantly, and Q was less than 0.3 (Q <1 for synergy). The results of fluorescence staining and cell scratch test showed that, compared with the solvent control group, the apoptosis rate of B-9-3 (25 and 200 g/mL) group increased significantly, and the rate of scratch repairing decreased significantly (P <0.01). Conclusion B-9-3 inhibits the migration of LLC cells and increases the rate of apoptosis significantly, and has synergistic effect with the combination of different antitumor drugs.
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[基金项目]
兵团中青年科技创新领军人才计划(2015BC001)