Korean J Pathol.  1999 Feb;33(2):71-79.

The Effects of Transforming Growth Factor beta1 on Apoptosis in Rat Hepatocellular Carcinoma

• Park YE
• Choi YH
• Lee WY
• Park JJ
• Choi KC
• Shin HS

Abstract

Based upon the concept that carcinogenesis is associated with apoptosis, specific therapies designed to enhance the susceptibility of cancer cells to undergo apoptosis could be developed. Thus, in this paper, it was designed to investigate whether, using rat animal model with chemical-induced hepatocellular carcinoma, TGF-1 in vivo could induce apoptosis in cancer. The chemical hepatocarcinogenic procedure of Solt-Farber method was used on Sprague-Dawley rats. Experimental groups were divided into group A treated with the standard Solt-Farber regimen of diethylnitrosamine (DEN) and 2-Acetaminofluorene (AAF), group B TGF-, group C TGF-1, and group D adriamycin after hepatocellular carcinoma developed. For detection of apoptotic cells, apoptotic indices were examined by the in situ end DNA labelling method. The expression of proliferating cell nuclear antigen was examined by immunohistochemical staining. Apoptosis of rat hepatocellular carcinoma cells increased significantly to 4.92+/-2.32/HPF in the group C compared with the control group (A) (2.54+/-1.13/HPF; P<0.05). Two distinctly different populations of proliferating hepatocellular carcinoma cells were identified. The cells at G1/S boundary (weak granular staining) increased to 15.75+/-6.19/HPF and 6.45+/-2.93/HPF in the groups C and D, respectively, but decreased to 2.42+/-2.06/HPF in the group B compared with the control group (A) (6.38+/-2.18/HPF; p<0.05). The cells at S phase (strong granular staining) increased to 3.37+/-2.69/HPF in the group B but decreased to 0.32+/-0.47/HPF in the group D (p<0.05). In conclusion, these results indicate that the TGF-1 may be used as an effective anticancer agent.

Keyword

Rat; Apoptosis; TGF-beta1; TGF-alpha; Hepatocellular carcinoma

MeSH Terms

Animals
Apoptosis
Carcinogenesis
Carcinoma, Hepatocellular*
Diethylnitrosamine
DNA
Doxorubicin
Models, Animal
Proliferating Cell Nuclear Antigen
Rats*
Rats, Sprague-Dawley
S Phase
Transforming Growth Factor alpha
Transforming Growth Factor beta1*
Transforming Growth Factors*
DNA
Diethylnitrosamine
Doxorubicin
Proliferating Cell Nuclear Antigen
Transforming Growth Factor alpha
Transforming Growth Factor beta1
Transforming Growth Factors