Effects Of AG490 On Leptin And JAK2/STAT3 Signal Pathway In Transplanted Tumor Of Nude Mice With Human Gastric Cancer

Objective: We aimed to explore the effects of Leptin and JAK2/STAT3 signal pathway on the growth of transplanted tumor of nude mice with human gastric cancer intervened by AG490 which was the retardant to JAK2/STAT3 signal pathway and its relationship with the expression of genes and protein.Methods: The models of transplanted tumor of BALB/c-nu male nude mice with SGC-7901 human gastric cancer cells were established,then 30 model mice were randomly divided into 3 groups.The mice of group A were the normal control group,and were induced by intraperitoneal injection of normal saline.The mice of group B were induced by intraperitoneal injection of AG490(8mg/kg).The mice of group C were induced by intraperitoneal injection of 5-FU(50mg/kg).The intraperitoneal injection of AG490 and 5-FU was once every 3 days,a total of 4 times,and nude mice were killed the day after drug withdrawal.The tumor weight was recorded,and the inhibiting rates of growth of transplanted tumor were calculated.The pathology slice of the tumor was made.The expressions of the Leptin ? JAK2 and STAT3 genes and protein were detected by RT-PCR technique and immunohistochemistry.Results:(1)Tumor general situation: compared with the control group A,the nude mice tumor weight of group B and group C decreased obviously(P<0.05),and in comparison between group B and group C,there was no statistical difference(P>0.05).(2)The pathology slice of the tumor: the tumor cells growth of group A was relatively strong,and the area of tumor cell necrosis of group A was samller than group B and group C.(3)RT-PCR results: interms of the expression of Leptin mRNA level,compared with group A,the Leptin expression level of group B and group C decreased significantly(P<0.01),and in comparison between group B and group C,there was no statistical difference(P>0.05).In m RNA expression level of JAK2,compared with group A,the JAK2 mRNA expression level of group B decreased significantly(P<0.01),and the JAK2 mRNA expression level of group C increased slightly(P=0.028<0.05).In terms of the m RNA expression level of STAT3,compared with group A,the STAT3 mRNA expression level of group B decreased significantly(P<0.01),and there was no statistically significant difference between group A and group C(P>0.05).(4)Immunohistochemistry results: in terms of the expression of Leptin protein level,compared with group A,the Leptin expression level of group B and group C decreased significantly(P<0.01),and in comparison between group B and group C,there was no statistical difference(P>0.05).In protein expression levels of JAK2,compared with group A,the JAK2 protein expression level of group B decreased significantly(P<0.01);There was no statistically significant difference between group A and C(P>0.05).In terms of the protein expression level of STAT3,compared with group A,the STAT3 protein expression level of group B decreased significantly(P<0.05),and there was no statistically significant difference between group A and C(P>0.05).Conclusion: The high expression of Leptin gene may be correlated with growth of human gastric cancer.AG490 and 5-FU has the function of inhibiting gastric cancer cell proliferation,and AG490 could lower the expression of the Leptin gene by inhibiting JAK2/STAT3 signal pathway.Meanwhile,there may be other mode to adjust the expression of the Leptin gene.