Effect of naloxone in combination with morphine on the growth of subcutaneous tumor of human gastric cancer MGC-803 cells in nude mice / 临床麻醉学杂志

ABSTRACT

Objective To observe the effects of naloxone in combination with morphine on the growth of subcutaneous tumor of human gastric cancer MGC-803 cells in nude mice.Methods The model of subcutaneous tumor of human gastric cancer MGC-803 cells in nude mice was established.Fifty nude mice were randomly divided into 5 groups control group (group C),normal saline group (group S),20 mg/kg morphine group (group M),and 1 mg/kg naloxone group (group N),and 1 mg/kg naloxone+20 mg/kg morphine group (group NM).The mice in group C received no treatment,while the mice in group S,group M,group N and group NM were injected with 1.5 ml/kg saline,20 mg/kg morphine,1 mg/kg naloxone,and 1 mg/kg naloxone+20 mg/kg morphine per day,respectively.The caliper was used to measure the tumor sizes every the other day.The mice in each group received intraperitoneal injection of the drugs for 2 week.Then the relative volume (RTV) of tumor was calculated.The expression of Cyclin D1,VEGF,MMP-9 mRNA and proteins were detected by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR),immunochemistry staining and Western blot.Results RTV in group M (2.21±0.62)% was significantly lower than that in group C (3.16±0.68)%,group S (2.98±0.61)%,group N (3.16±0.35)% and group NM (2.64±0.37)% (P<0.05).RTV in group NM was significantly lower than that in group C,group S and group N (P<0.05).Compared with group C,the expression of Cyclin D1,VEGF,and MMP-9 in group M were significantly decreased (P<0.05).The organizational structure of the subcutaneous tumor in groups C,S,N and NM was almost normal.Cytoplasm vacuolization,disruption of nuclear membrane and chromatin margination were occured in group M.While the level of Cyclin D1,VEGF,and MMP-9 in group NM was increased compared to group M (P<0.05).Conclusion Morphine could inhibit the growth of subcutaneous tumor of human gastric cancer MGC-803 cells in nude mice by downregulating the expression of Cyclin D1,VEGF,and MMP-9.Naloxone could antagonize the anti-growth effects of morphine.