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),and no significant change was found in each parameter mentioned above in group NS (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.

Objective To evaluate the role of opioid receptors in fentanyl-induced inhibition of proliferation and migration of human gastric cancer cell line MGC-803.Methods The human gastric cancer cell line MGC-803 was cultured in DMEM liquid culture medium.The cells were seeded in 6-well or 96-well plates and then randomly divided into 4 groups (n =54 each):control group (group C),fentanyl group (group F),naloxon group (group N) and naloxon + fentanyl group (group NF).The cells were exposed to 0.1 μmol/L fentanyl and 10 μmol/L naloxon in F and N groups,respectively.The cells were incubated with 10 μmnol/L naloxon for 30 min and then O.1 μmol/L fentanyl was added to the culture medium in group NF.The viability of the cells was detected by MTT assay after being incubated with fentanyl for 12,24,36,48,60 and 72 h.The cell apoptosis was assessed by flow cytometry after being incubated with fentanyl for 24 h.The migration of the cells was detected by wound healing assay after being incubated with fentanyl for 48 h.The proliferation of the cells was determined by colony formation assay at 7 day of incubation with fentanyl.Results Compared with group C,no significant changes in the viability of the cells,rate of colony formation,apoptotic rate and rate of cell wound healing were found in group N (P ＞ 0.05),and the viability of the cells,rate of colony formation and rate of cell wound healing were significantly decreased,and the apoptotic rate was increased in F and NF groups (P ＜ 0.05).There was no significant difference in the viability of the cells,rate of colony formation,rate of cell wound healing and apoptotic rate between group NF and group F (P ＞ 0.05).Conclusion Opioid receptors are not involved in fentanyl-induced inhibition of proliferation and migration of human gastric cancer cell line MGC-803 in vitro.