Fentanyl Citrate Influence On The Growth Of Subcutaneous Tumor Of Human Gastric Cancer In Nude Mice

Objective: To observe the effects of fentanyl citrate on the growth ofsubcutaneous tumor of human gastric cancer in nude mice.Methods: Cultured MGC-803cell in vitro, and the preparation of thelogarithmic phase cells suspension, inoculated subcutaneously in right-oxter inevery nude mice, and then the model of subcutaneous tumor of human gastriccancer in nude mice were established. Modeling after eliminate subcutaneoustumors had the maximum and minimum of two nude mice, the remaining30nude mice randomly divided into6groups by the random number table method:control group(group C), normal saline group(1.5ml/kg N), group F1(0.05mg/kg fentanyl), group F2(0.1mg/kg fentanyl), group F3(0.2mg/kgfentanyl), and group F4(0.4mg/kg fentanyl), there were5mices in each group.After the tumor diameter reached to1.0cm×1.0cm in length and width, groupC received no treatment, while group N, group F1, group F2, group F3, groupF4were injected1.5ml/kg saline,0.05mg/kg fentanyl,0.1mg/kg fentanyl,0.2mg/kg fentanyl,0.4mg/kg fentanyl, respectively per day. The solutions for all the groups were injected intraperitoneal. After14days, the nude mice werekilled by pulling neck, and the tumor was completely stripped. The tumorvolume was determined using a caliper, calculating the relative volume(RTV)and depicting tumor growth curve. Transmission electron microscope(TEM)observe morphological changes of tumor tissue; immunochemistry staininganalyze the expression of NF-κB, Bcl-2, Bax, VEGF, MMP-9in subcutaneoustumor tissue; The expression of NF-κB, Bcl-2, Bax, VEGF, MMP-9mRNA andproteins were detected by semi-quantitative reverse transcription polymerasechain reaction(RT-PCR) and Western blot.Results: Comparing with group C(3.36±0.68), tumor relative volume(RTV)of group F1, group F2, group F3, group F4were(2.03±0.52),(2.09±0.46),(2.25±0.26),(2.56±0.54) respectively，and the RTV of N group was (3.19±0.60).RTV infentanyl groups were significantly less than that in group C (P＜0.05).The structure of subcutaneous tumor cells and synapsis was normal in C group,N group；group F1, group F2, group F3and group F4showed nuclear swelling,chromatin condensation, chromatin reduced, nuclear fragmentation insubcutaneous tumor cells. Compared with group C, NF-κB-positive,Bcl-2-positive, VEGF-positive, MMP-9-positive stained subcutaneous tumorcells were deceased, while Bax-positive subcutaneous tumor cells wereincreased in group F1, group F2, group F3and group F4. Group N comparedwith group C, There was no significant difference of integral optical densityvalues（P＞0.05）. RT-PCR and Western blot showed: Compared with group C,the NF-κB, Bcl-2, VEGF, MMP-9mRNA and protein expression ofsubcutaneous tumor in F1, F2, F3, F4groups were down-regulated, while BaxmRNA and protein expression were up-regulated. Group N compared withgroup C, There was no significant difference of mRNA and protein expression （P＞0.05）.Conclusions: Fentanyl citrate plays a role in inhibiting the growth ofsubcutaneous tumor of human gastric cancer in nude mice,its mechanism mightbe through inhibiting the expression of NF-κB then change the ratio ofBcl-2/Bax (reduced the expression of Bcl-2and increased the expression ofBax)and lower the expression of VEGF, MMP-9.