阿西替尼与多柔比星协同抗肿瘤活性研究

Synergistic anti-tumor effects of axitinib and doxorubicin

为了研究阿西替尼与多柔比星的协同抗肿瘤活性,在体外用不同浓度的阿西替尼与多柔比星混合溶液处理人肺腺癌A549细胞株,以MTT法测定药物对肿瘤细胞及肿瘤球的生长抑制率,考察其协同作用。通过细胞摄取实验、细胞周期分布实验及DNA ladder实验对阿西替尼与多柔比星协同作用的机制进行初步探索。以A549实体瘤荷瘤裸鼠为模型,考察阿西替尼与多柔比星联合应用的体内抗肿瘤效果。结果显示,阿西替尼与多柔比星联用具有高度协同的抗肿瘤效果,其体外细胞毒性显著强于两种药物单独使用,且对肿瘤细胞和肿瘤球的生长抑制作用呈现时间-浓度依赖性;体内研究表明,阿西替尼与多柔比星联合使用能够显著抑制荷瘤裸鼠的肿瘤生长,且其抑瘤效果显著优于两药单独使用。

To study the synergistic anti-tumor effects of doxorubicin and axitinib in combination, and investigate the underlying mechanism, we performed the MTT cytotoxic assay and tumor spheroids inhibition to investigate in vitro using A549 cells. The cell internalization, cell cycle distribution and DNA ladder experiments were performed to study the synergistic mechanisms. A549 xenograft was established in nude mice and adopted to study the in vivo anti-tumor effect of doxorubicin and axitinib. Results showed that combination of doxorubicin and axitinib exerted significantly higher cytotoxicity than each single drug, and induced a synergistic effect on tumor spheroids growth inhibition. The combination achieved the highest tumor growth suppression in vivo in the A549 xenograft. The combination of axitinib and doxorubicin exhibited the best anti-tumor effects both in vitro and in vivo than each single drug.