[Influence of p16 gene on the biological behavior of human hepatocellular carcinoma].
OBJECTIVE
Inactivation of the tumor suppressor gene p16INK4a is one of the most common genetic alterations in human hepatocellular carcinomas (HCC), making it an ideal target gene for treatment of HCC. The objective of this study was to investigate the influence of wild p16 gene on the biological behavior of HCC.


METHODS
HCC cell strains SNU-449 (loss of p16 protein expression) and HepG2.2. 15 (positive p16 protein expression) were respectively infected by a retrovirus expression vector of p16 gene (pcLXSN-p16). The stable p16 protein expression cell strains were selected. The biological behaviors of the p16 gene transfected HCC cells were observed.


RESULTS
SNU-449 with negative p16 protein expression demonstrated that pcLXSN-p16 treatment significantly inhibited cell growth (the amount of cells at G0-G1 phase increased). However, there was no treatment effect when pcLXSN-p16 was transfected in HepG2.2. 15 which has positive p16 protein expression. Subsequent study in a nude mouse model demonstrated that the p16 gene transfected SNU-449 had a lower succeeding rate of first time establishment of tumors and grew more slowly in the nude mice as compared with non-transfected SNU-449. Moreover, the nude mice inoculated with transfected SNU-449 had a longer survival time than those inoculated with non-transfected SNU-449.


CONCLUSIONS
The transfer of wild p16 gene can inhibit the proliferation and reduce the invasion ability of HCC cells with p16 negative expression, but can not affect the HCC cells with p16 positive expression.
Huang
Jian-Zhao
JZ
Department of Hepatobiliary Surgery, Daping Hospital, Third Military Medical University, Chongqing, Sichuan, 400042, P. R. China. hjz999@mail.tmmu.com.cn
Xia
Sui-Sheng
SS
Ye
Qi-Fa
QF
Jiang
Han-Ying
HY
D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D019942:Genes, p16; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009368:Neoplasm Transplantation; D012190:Retroviridae / Q000235:genetics; D014162:Transfection
D019941:Cyclin-Dependent Kinase Inhibitor p16