Effect of rosiglitazone combined with all-trans retinoic acid on anti-angiogenesis of transplanted gastric cancer in nude mice / 中华消化杂志

ABSTRACT

Objective To investigate the effect of rosiglitazone (ROS),a peroxisome poliferator- activated receptor (PPAR)?ligand,combined with all-trans retinoic acid (ATRA) on anti-angiogenesis of transplanted gastric cancer in nude mice,and to explore the mechanism of anti-angiogenesis prelimina- rily.Methods The model of xenograft tumor in nude mice were established by inoculating human gastric cancer cells line MGC803 (lower differentiated) into the back of nude mice subcutaneously.The cancer- bearing nude mice were divided randomly into 5 groupsgroup 1 (n=6) with no treatment;ROS treat- ment (group 2,n=6),ROS combined ATRA treatment includinglow dose treatment (group 3,n= 6),moderate dose treatment (group 4,n=6) and high dose treatment (group 5,n=6).After treated for forty days,the volume change of tumor and tumor inhibition rates were observed.The expression of CD34,vascular endothelial growth factor (VEGF) in grafts were detected by immunohistochemical and calculated the difference of MVD.The mRNA expression levels of VEGF,HIF-l?were detected by RT- PCR assay accordingly.Results①The volume of tumor was significantly decreased in ROS treatment group compared with group 1 (P＜0.01).The tumor inhibition rates of group 2 were similar to group 3 (P＞0.05).With the increasing of the dose of ROS the tumor inhibition rates were increased.They were dose-dependent in specified dose-range.②ROS could inhibit angiogenesis of xenograft tumor and depress expression of mRNA of VEGF and HIF-l?.When ROS combined with ATRA,the increasing of dose of ROS,inhibiting angiogenesis of tumor and depressing expression of mRNA of VEGF and HIF-l?were found (P＜0.05).Conclusion ROS (25 mg?kg?2 d~(-1)) can inhibit the growth of tumor,and ROS combined with ATRA can further inhibit the growth of tumor,which may be through the path of PTEN by inhibiting the angiogenesis of tumor