ABSTRACT
Hepatocellular carcinoma (HCC) is the most common lethal malignancy and a leading cause of malignancy-associated death in many countries, but mainly in Asia. Expression of the NAD(P)H:quinone oxidoreductase 1 (NQO1) protein is involved in the growth of various human cancers, including HCC. NQO1 is considered an inhibitor of cancers. The present study aimed to investigate the function and mechanism of NQO1 in HCC. In this study, we found that NQO1 overexpression decreased HCC cell SK-hep-1 and Hep3B cell proliferation and induced apoptosis. The apoptosis-associated gene Bax, Bcl-2, and caspase-3 expression was also measured, with western blot results showing that NQO1 overexpression inhibits Bcl-2 expression and promotes Bax and caspase-3 expression, whereas NQO1 silencing plays a contrasting role. In addition, NQO1 activated AMP-activated protein kinase (AMPK) and proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and the AMPK inhibitor compound C blocked NQO1-induced PGC-1α activation. Furthermore, the AMPK inhibitor compound C or PGC-1α siRNA partially abolished NQO1-induced cell apoptosis and proliferation inhibition in HCC cells. Taken together, our results demonstrate that NQO1 overexpression induces HCC cell apoptosis and proliferation inhibition through the AMPK/PGC-1α pathway.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Carcinoma, Hepatocellular/enzymology , Liver Neoplasms/enzymology , NAD(P)H Dehydrogenase (Quinone)/metabolism , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism , Apoptosis , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation , Cell Survival , Enzyme Activation , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , NAD(P)H Dehydrogenase (Quinone)/physiologyABSTRACT
OBJECTIVE: To investigate the expression and significance of Glypican-3 in colorectal cancer. METHODS: Immunohistochemistry was used to detect the expression of Glypican-3 in 200 specimens of colorectal cancer and adjacent non-cancerous tissues resected during operation. RESULTS: Glypican-3 immunoreactivity was recognized in both the cytoplasm and cellular membrane. The Glypican-3 positive expression rate in the tumor samples was 66.0% (132/200), significantly higher than that in the adjacent nontumor tissues (24%, 48/200, P = 0.019). The Glypican-3 expression rate was significantly correlated with the carcinoma invasion (P = 0.023) and lymph node metastasis (P = 0.015), but not associated with gender, age, tumor size, and differentiation grade (all P > 0.05). CONCLUSION: Over-expression of Glypican-3 may play an important role in the genesis and development of colorectal cancer, and may be used as a new biological parameter in predicting invasion and metastasis of colorectal carcinoma.
