Enhanced proliferation inhibition and apoptosis in glioma cells elicited by combination of irinotecan and imatinib
Enhanced proliferation inhibition and apoptosis in glioma cells elicited by combination of irinotecan and imatinib
复制标题
伊立替康和伊马替尼联合使用可增强胶质瘤细胞的增殖抑制和凋亡
DOI：
10.1016/j.ejphar.2020.173022
复制
发表时间：
2020-05-05
影响因子：
5
通讯作者：
Luo, Peihua
中科院分区：
文献类型：
--
作者：
Lu, Jiabin;Hu, Yuhuai;Luo, Peihua
Glioma is a kind of lethal malignant tumor, and lacks efficient therapies. Combination therapy has been claimed to be a promising approach to combat cancer, due to its increased anti-cancer effects and reduced side effects. This study aimed to investigate the anti-cancer effect and mechanism of combining imatinib with irinotecan or its active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38). First, we found that this drug combination exerted synergistic antitumor effects against glioma in vitro and in vivo. In addition, flow cytometry results proved that the SN-38-induced apoptosis was further enhanced by imatinib, and similar results were observed by determining the protein expression levels of apoptosis biomarkers. Interestingly, p53 expression was elevated by the SN-38 mono-treatment, and was not further increased after the co-treatment; besides, knockdown of p53 could only reduce the expression of cleaved-PARP partially, and weaken the enhanced proliferation inhibition induced by SN-38 plus imatinib, indicating that there might be other factors involved in the synergistic effects besides p53. Meanwhile, the markedly elevated p21 expression was observed only in the combination group, instead of the mono-treated groups. According to the results of p21 knockdown, we found that p21 was also required for the synergistic inhibitory effects. Moreover, we explored and ruled out the possibility of imatinib enhancing the sensitivity of irinotecan by inhibiting drug efflux pumps. Thus, our findings collectively suggest that combining irinotecan with imatinib could be a promising new strategy to fight against glioma.
