The results showed that p53 over-expression is a reliable marker for mutational modulation of p53 function. p53 was negatively correlated with p21/WAF1 in hepatitis B virus-related HCC (p=0.024, r=-0.432).
The p21(WAF1/CIP1) labeling index was significantly higher in cirrhosis than in normal livers (P=0.024) and markedly decreased in low-grade dysplastic nodules, high-grade dysplastic nodules, and hepatocellular carcinomas compared with cirrhosis (P<0.05).
These effects were accompanied by downregulation of proteins involved in anti-apoptosis (Bcl-xL, XIAP or c-IAP2) and cell-cycle progression (cyclin D1), and induction of proteins involved in pro-apoptosis (Bax) and cell-cycle retardation (p21Waf1/Cip1), although the degree of changes by DHMEQ was different in each hepatoma cell type.
In this study, we first demonstrated that TF (5-30 microM) induced apoptosis in several types of human cancer cell lines including human hepatoma (Hep G2), colorectal cancer (COLO 205), and fibroblast (CCD 922SK) cells for 24 h. The cellular responses to TF-induced apoptosis were demonstrated to be associated with the p53-signaling pathway, including induction of p53, p21/Cip1, p27/Kip1, bax protein expression and inhibition of bcl-2 protein expression.
To elucidate new regulatory mechanisms for heptocarcinogenesis, we investigated the regulation of p21, a cyclin-dependent kinase (CDK) inhibitor encoded by CDKN1A, in HCC.
CONCLUSIONS We found that JUN, EGR1, MYC, and CDKN1A might be used as diagnostic and therapeutic molecular biomarkers and broaden our understanding of the molecular mechanisms of HCC.
The transcriptional induction of plasminogen activator inhibitor-1 and p21(WAF1/CIP1) by TGF-beta were detected in all HCC cell lines, implying that the molecular integrity of the TGF-beta receptors might be intact.
Our data indicate that p21(CIP2/Waf1) overexpression may not be the only regulatory factor necessary for RA-induced apoptosis in human hepatoma Hep3B cells.
Molecular mechanism of cell cycle blockage of hepatoma SK-Hep-1 cells by Epimedin C through suppression of mitogen-activated protein kinase activation and increased expression of CDK inhibitors p21(Cip1) and p27(Kip1).
Moreover, proliferation index of 60 human HCCs was inversely correlated with protein levels but not with mRNA levels of P21(WAF1), P27(KIP1), P57(KIP2) and P130, indicating a control of human HCC proliferation by posttranslational modifications of cell cycle regulators.
After the transfection of alpha-1,3-fucosyltransferase (FucT)-VII cDNA into H7721 human hepatocarcinoma cells, the protein expression of some cyclins, cyclin-dependent kinases (CDKs) and cyclin-dependent kinase inhibitors (CDIs) p16INK4 and p21waf1/Cip1 were unchanged.
These findings raise the potential that forced upregulation of p21(WAF1/CIP1) in hepatocellular carcinoma (HCC) may reduce the doses of cisplatin to achieve similar responses and suggest the possible use of p21(WAF1/CIP1) in HCC treatment.
The positive rate of HBcAg expression in cancerous tissues of 40 HCCs was 20.0%, which was also lower than that in para-cancerous and adjacent normal liver tissues (chi2 = 9.482, P < 0.01; chi2 = 14.645, P < 0.01). p21 protein deletion rate in cancerous tissues of 40 HCCs was 27.5%, which was higher than that in para-cancerous and adjacent normal liver tissues (chi2 = 7.439, P < 0.01; chi2 = 11.174, P < 0.01). p21 protein deletion correlated remarkably with the pathological grade of HCC (chi2 = 0.072, P < 0.05).
Pharmacological or transcriptional inhibition of both HDAC1 and 2 leads to cell cycle blockage and apoptosis via p21<sup>Waf1/Cip1</sup> and p19<sup>INK4d</sup> upregulation in hepatocellular carcinoma.
We previously reported that overexpression of integrin beta1 subunit imposed a growth inhibitory effect on the hepatocellular carcinoma cell line SMMC-7721 through transcriptional activation of p21(WAF1/CIP1) gene.
Our study has provided molecular evidence to demonstrate that wogonin and fisetin had effective cytotoxic effects through apoptosis induction in hepatocellular carcinoma cells SK-HEP-1; activation of caspase 3 cascade, induction of p53 protein and alternative expression of p21(Waf/Cip-1) protein were involved.