The Influence Of FABP5/PPAR?/? Pathway To The Liver Tumor Development Of Transgenic Mice Induced By H-Ras12V

Objective : To investigate the influence of FABP5/PPAR?/? pathways in Ras oncogene-induced liver tumor.And provide effective basic data for prevention and treatment of liver cancer.Methods:1.In vivo experimentsThe liver tumor tissues and peri-tumor tissues of 9-month-old H-Ras12 V transgenic male mice and normal liver tissues of C57BL/6J male mice were sampled.The m RNA level of FABP5,PPAR?/?,ILK,PDK1 were examined by RT-q PCR.The protein levels of ERK1/2,p-ERK1/2,PI3 K,p-PI3 K,AKT,p-AKT,NF-?B,p-NF-?B,I-?B,FABP5,and PPAR?/? were detected by Western blot.2.In vitro experimentsThe total protein were extracted from LO2 and Hep3 B cell lines.The protein levels of p-PI3 K,PI3K,p-AKT,AKT and I-?B were detected by Western blot.The inhibitors were used to inhibit the activities of PI3 K and AKT in Hep3 B cells respectively,and protein NF-?B and FABP5 were detected.Results:1.In vivo experiments(1)Compared with the liver of non-transgenic mouse,the liver of H-Ras12 V transgenic mouse harbored hepatic tumors.The pathology analysis showed that the hepatic tumor tissues exhibited trabecular growth arrangement,atypical liver cell aggregation,cytoplasmic basophila,hyperchromatic nuclei and contained highly undifferentiated cells accompanied by necrosis.The fibrosis and cirrhosis were not observed.(2)Compared with the normal liver tissues and peri-tumor tissues,the protein level of PPAR?/? was significantly reduced(P<0.05)in tumor tissues.But,the protein level of PPAR?/? in normal liver tissues was significantly higher than peri-tumor tissues.However,compared with the normal liver tissues and peri-tumor tissues,the m RNA level of PPAR?/? was higher(P<0.05)in tumor tissues.But,there was no significant difference between normal liver tissues peri-tumor tissues and tumor tissues.(3)Compared with the normal liver tissues and peri-tumor tissues,the phosphorylation and total protein levels of ERK were significantly increased(P<0.05).There was no significant difference between normal liver tissues and peri-tumor tissues in ERK level.However,the p-ERK level was significantly increased in peri-tumor tissues(P<0.05).Compared with the normal liver tissues and peri-tumor tissues,the protein levels of PI3 K,p-PI3 K,p-AKT,p-NF-?B,Nucle-NF-?B and FABP5 were significantly increased(P<0.05).NF-?B,Quality-NF-?B,I-?B and PPAR?/? were significantly reduced(P<0.05)in tumor tissues.There was no significantly difference between normal liver tissues and peri-tumor tissues in p-PI3 K,NF-?B,Quality-NF-?B and I-?B levels.2.In vitro experiments(1)Compared to LO2,the protein level of PPAR?/? was significantly increased.(2)There was no significantly difference between Hep3 B and LO2 in p-PI3 K and I-?B level.But,compared to LO2,the protein level of PI3 K was significantly decreased in Hep3 B.(3)In Hep3 B cells,inhibiting PI3 K activity by LY significantly decreased the protein level of FABP5.Its protein level also decreased between 24 h to 48 h.And.inhibiting AKT activity by MK significantly decreased the protein level of FABP5,as well.Conclusions:1.In the development of the liver tumorigenesis induced by H-Ras12 V,the activation of MAPK/ERK,PI3K/AKT and NF-?B signaling pathways may contribute to the overexpression of FABP5.But the synergies between them need to be further studied.2.The level of FABP5 is mainly regulated by PI3 K and AKT in Hep3 B cells.