Key result
The combination of doxorubicin and chloroquine had a significantly stronger anti-angiogenic effect than doxorubicin alone or thalidomide in vitro and in vivo.
Why the study?
Does the combination of chloroquine and doxorubicin synergistically suppress angiogenesis in vitro and in vivo?
Does the combination of chloroquine and doxorubicin synergistically suppress angiogenesis in vitro and in vivo?
Chloroquine enhances the anti-angiogenic effect of doxorubicin in preclinical models, suggesting a potential strategy to overcome resistance to anti-angiogenic therapy.
Combination may enhance doxorubicin effects on endothelial cells in vitro; leaves open clinical translation for resistance.
BACKGROUND: The inhibition of autophagy using pharmacological inhibitors such as chloroquine may be an effective strategy to overcome chemotherapy or resistance to anti-angiogenic therapy. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: Chloroquine enhanced the anti-angiogenic effect of doxorubicin on CAM at the tested concentrations.
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Gürel-Gürevin et al. (2018) studied Angiogenesis. Chloroquine and doxorubicin combination vs. Doxorubicin alone and positive control (±)-thalidomide was evaluated on Anti-angiogenic effect in CAM assay and in vitro tube-formation assay. The combination of doxorubicin and chloroquine had a significantly stronger anti-angiogenic effect than doxorubicin alone or thalidomide in vitro and in vivo.
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