Effects And Mechanism Of Interleukin-9 On The Growth Of Tumors Of Nude Mouse Model Of Human Pancreatic Cancer

OBJECTIVE To investigate the effect and mechanism of interleukin-9(IL-9)on human pancreatic cancer xenograft in nude mice.METHODS Human pancreatic cancer PANC-1 cells were inoculated subcutaneously into BALB/c(nu/nu)mice.When tumor xenografts reached about 50mm3,64 mice were random Ly divided into 4 groups(n=16 in each group)with injection of saline and different dose of IL-9(90 ng or 180 ng or360 ng)respectively every other day for 16 days.The tumor diameter was measured every 3 days.8 mice of each group were sacrificed random Ly on 3th day after the last treatment to measure the weight of tumor.The expression of IL-9R,JAK1,JAK3 and STAT3 m RNA in xenograft were examined by RT-PCR.The expression of STAT3 and p STAT3 were detected by immunohistochemistry and Western blotting.Cyclin D1 and Bcl-2 expression was assessed with immunohistochemistry and quantitated.The survival time of the rest mice were recorded and compared.RESULTS The mean weight of tumors in the control group,the low-dose group,the moderate-dose and the high-dose group were(196.75±25.32)mg,(216.01±37.15)mg,(261.63±39.85)mg and(323.12±46.71)mg respectively and increased in a dose-dependent manner.The weight of tumor in the moderate-dose and high-dose group was the most obvious higher as compared to the control group(P<0.05).The average survival time of the high-dose group was(33.3±4.9)d,which was significantly shortened compared with the other groups(P<0.05).There was no significant difference in expression of IL-9R,JAK1,JAK3 and STAT3 m RNA in each group(P>0.05).The result of Western blotting and immunohistochemical staining showed that after being treated with different doses of IL-9,the expression of p STAT3 in tumor tissue was significantly higher than the control group(P<0.05).The expression of STAT3 in all IL-9-treated groups have no significant difference compared with the control group(P>0.05).Immunohistochemical staining also showed that treatment of tumor tissues with different doses of IL-9 increased Cyclin D1expression(P<0.05),while Bcl-2 expression have no significant changes(P>0.05).CONCLUSIONS IL-9 can significantly promote the growth of subcutaneous transplanted tumor derived from human pancreatic cancer PANC-1 cells and reduce the survival time of the nude mice.The mechanism might be related to activation of STAT3 pathway.