Published online Apr 28, 2019. doi: 10.3748/wjg.v25.i16.1936
Peer-review started: January 27, 2019
First decision: February 26, 2019
Revised: March 7, 2019
Accepted: March 24, 2019
Article in press: March 25, 2019
Published online: April 28, 2019
Hepatocellular carcinoma (HCC) is the fifth common malignant tumor worldwide and has a poor prognosis. HCC is closely associated with the potential precancerous lesions. Early treatment at the precancerous stage could significantly prevent the occurrence of HCC. Signal transducer and activator of transcription 3 (STAT3) and pyruvate kinase M2 (PKM2) can be activated and enhance the Warburg effect in HCC. However, whether activation of STAT3 enhances the Warburg effect in liver precancerous lesions in rats, and the relationship between STAT3 and PKM2 remain unclear. Hence, clarifying the mechanism of liver precancerous lesion of HCC are very important.
Investigating the mechanism of STAT3 and the Warburg effect in liver precancerous lesions in rats may suggest potential molecular mechanisms of hepatocellular carcinogenesis, and further offer the potential for developing novel therapeutic strategies for HCC treatment.
To measure the expression of STAT3 and PKM2, and the Warburg effect in liver precancerous lesions in rats and in transformed WB-F344 cells, and to investigate the possible molecular mechanisms of STAT3 in liver precancerous lesions.
The Solt-Farber model is an established hepatic precancerous animal model. The transformed WB-F344 cells were induced with N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) and hydrogen peroxide (H2O2). The contents of glucose and lactate in the tissue and culture medium of the cells were detected with a spectrophotometer. The protein levels were examined by Western blot and immunofluorescence.
Here, we provide the evidence that the Warburg effect was enhanced in liver precancerous lesions in rats, perhaps through high expression of PKM2 and p-STAT3 in activated oval cells. STAT3 activation promotes the Warburg effect by activating PKM2 in transformed WB-F344 cells induced with MNNG and H2O2.
STAT3 activation promotes the Warburg effect by enhancing the phosphorylation of PKM2 in transformed WB-F344 cells. The Warburg effect, PKM2 and STAT3 expression were increased in liver precancerous lesions in rats.
We have carried out some rat experiments and in vitro cell experiments, but further studies are needed to explore the mechanism of liver precancerous lesions. We also need to collect clinical samples for further validation. STAT3 and PKM2 may be potential diagnostic or therapeutic targets and used for clinical diagnosis and therapy in the future.