Effect of fentanyl on expression of VEGF-A and MMP-9 in subcutaneous tumor of human gastric cancer in nude mice

Abstract

Objective To evaluate the effect of fentanyl on the expression of vascular endothelial growth factor A (VEGF-A) and matrix metallopeptidase-9 (MMP-9) in the subcutaneous tumor of human gastric cancer in nude mice. Methods Thirty SPF male BALB/C nude mice, aged 4-5 weeks, weighing 15-20 g, in which the model of subcutaneous tumor of human gastric cancer cell line MGC-803 was established, were randomly divided into 6 groups (n=5 each) using a random number table: control group (C group), normal saline group (NS group) and fentanyl 0.05, 0.10, 0.20 and 0.40 mg/kg groups (F1-4 groups). The mice in group C received no treatment.Fentanyl 0.05, 0.10, 0.20 and 0.40 mg/kg were intraperitoneally injected once a day for 14 consecutive days in F1-4 groups, respectively, while the equal volume of normal saline 1.5 ml/kg was given instead of fentanyl in group NS.The nude mice were sacrificed on 1 day after the end of administration, and the tumor tissues were obtained for examination of the ultrastructure of subcutaneous tumor (with a transmission electron microscope) and for detection of the expression of VEGF-A and MMP-9 (by immunohistochemistry and Western blot) and expression of VEGF-A and MMP-9 mRNA (by real-time reverse transcriptase polymerase chain reaction). Results No abnormality in the morphology of the subcutaneous tumor cells was observed in C and NS groups.The swollen nucleus, chromatin margination, nuclear fragmentation and apoptotic bodies were found in the subcutaneous tumor cells in F1-4 groups.Compared with group C, the expression of VEGF-A and MMP-9 protein and mRNA was significantly down-regulated in F1-4 groups (P 0.05). There was no significant difference in the expression of VEGF-A and MMP-9 protein and mRNA among F1-4 groups (P>0.05). Conclusion The mechanism by which fentanyl inhibits the growth and metastasis of subcutaneous tumor cells of human gastric cancer is related to down-regulation of VEGF-A and MMP-9 expression in nude mice. Key words: Fentanyl; Stomach neoplasms; Vascular endothelial growth factor A; Matrix metalloproteinase 9