Gurel-Gurevin Ebru, Kiyan Hulya Tuba, Esener Osman Behzat Burak, Aydinlik Seyma, Uvez Ayca, Ulukaya Engin, Dimas Konstantinos, Armutak Elif Ilkay
Department of Biology, Faculty of Science, Istanbul University, Istanbul, Turkey.
Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University, Eskisehir, Turkey.
Anticancer Res. 2018 Jul;38(7):4011-4020. doi: 10.21873/anticanres.12689.
The inhibition of autophagy using pharmacological inhibitors such as chloroquine may be an effective strategy to overcome chemotherapy or resistance to anti-angiogenic therapy.
The cytotoxic effect of doxorubicin (0.1-1 μM), chloroquine (0.25-32 μM) and their combination were investigated by employing ATP assay in human umbilical vein endothelial cells (HUVECs). The effect of doxorubicin and chloroquine combination was also measured using tube formation assay on Matrigel. The anti-angiogenic activities of doxorubicin (2.5 μg/pellet) and chloroquine (15 μg/pellet), their combination, and standards (50 μg/pellet) were tested in vivo using the chick embryo chorioallantoic membrane (CAM) assay.
The combination of doxorubicin and chloroquine significantly had a stronger anti-angiogenic effect than the positive control (±)-thalidomide and doxorubicin alone in the CAM assay and in vitro tube-formation assay.
Chloroquine enhanced the anti-angiogenic effect of doxorubicin on CAM at the tested concentrations.
使用氯喹等药物抑制剂抑制自噬可能是克服化疗或抗血管生成治疗耐药性的有效策略。
采用ATP检测法，研究阿霉素（0.1 - 1 μM）、氯喹（0.25 - 32 μM）及其组合对人脐静脉内皮细胞（HUVECs）的细胞毒性作用。还使用基质胶上的成管实验检测阿霉素与氯喹组合的效果。采用鸡胚绒毛尿囊膜（CAM）实验在体内检测阿霉素（2.5 μg/粒）、氯喹（15 μg/粒）、它们的组合以及标准品（50 μg/粒）的抗血管生成活性。
在CAM实验和体外成管实验中，阿霉素与氯喹的组合比阳性对照（±）-沙利度胺和单独使用阿霉素具有更强的抗血管生成作用。
在所测试的浓度下，氯喹增强了阿霉素对CAM的抗血管生成作用。
