Colorectal cancer cells refractory to anti-VEGF treatment are vulnerable to glycolytic blockade due to persistent impairment of mitochondria
发表时间：2013-12-18 13:23
Abstract
Antiangiogenesistherapyhasshednewlightoncancertreatment,butitseffectiveness,especiallyforoverall patient survival, is still controversial. Here, we show that antiangiogenesis treatment causes a persistent suppression of mitochondria biogenesis in colorectal cancer cells, which renders them more sensitive to glycolytic blockade therapy. We first analyzed bevacizumab-resistant colon cancer xenografts by two- dimensionalBlueNative/SDS-PAGEandfoundaseriousandpersistentlossofmitochondrialproteincomplex I.Furthermetabolicassaysrevealedsignificantlyimpairedmitochondrialfunctionandhyperactiveglycolysis, which were concomitant with the upregulation of HIF-1 and Hsp70. The treatment of bevacizumab-resistant cells with the glycolysis inhibitor 3-BrPA caused cell senescence in vitro. Intraperitoneal injection of 3-BrPA to xenograftmicebearingbevacizumab-resistantcellsalsoresultedinsmallertumorvolumeandlongersurvival. These data provide direct evidence for the mitochondrial destruction of bevacizumab-resistant tumor cells and suggest that glycolysis blockade may potentiate the therapeutic effect of antiangiogenesis treatment.
第一署名医院：仁济医院
