As a number of candidate genes of Bmi1 were identified in this st

As a number of candidate genes of Bmi1 were identified in this study, coordinated regulation of multiple Bmi1 targets might be needed to recapitulate Bmi1-mediated tumorigenesis in vivo. In this regard, knockdown of Sox17 or other candidate target genes in Ink4a/Arf−/−

Dlk+ cells would be intriguing to assess for their tumorigenic activity in vivo. Finally, our findings demonstrated Selleck GSK126 that Bmi1 regulates the self-renewal of hepatic stem/progenitor cells to a large extent through the suppression of Ink4a/Arf. However, it is evident that targets of Bmi1 other than the Ink4a/Arf locus are also responsible for the development of cancer. Further analyses are necessary to determine the roles of the genes listed here in liver development, regeneration, and cancer. The authors thank Dr. M. van Lohuizen for Bmi1+/− mice, Dr. W. Pear for the MIGR1 vector,

Dr. Valentina M. Factor for the anti-A6 antibody, Dr. N. Nozaki for the anti-Bmi1 antibody, Dr. A. Miyawaki for Kusabira orange, Y. Yamazaki for technical support with the flow cytometry, and M. Tanemura for laboratory assistance. Additional Supporting Information may be found in the online version of this article. “
“Aim:  The human hepatocellular carcinoma (HCC) cell line HepG2 can easily acquire resistance to doxorubicin. However, the mechanism of action is unclear. Methods:  In the present study, we used confocal microscopy, flow cytometry and other methods to reveal the mechanisms by which HepG2 cells acquire doxorubicin resistance. Pexidartinib cost Results:  Our results showed that R-HepG2 cells, a doxorubicin-resistant sub-line of HepG2, exhibited decreased intracellular accumulation of doxorubicin and increased expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 when compared with HepG2 cells. R-HepG2 cells also harbored higher levels of glutathione and increased expression of glutathione peroxidase. Furthermore, we demonstrated that the phosphorylation of mitogen-activated protein kinases (p38 and c-jun-N-terminal kinases), IkBα and CREB were increased

in R-HepG2 cells. Specific p38 inhibitor SB203580 decreased P-gp Cisplatin manufacturer expression. The multi-kinase inhibitor sorafenib tosylate also significantly suppressed the phosphorylation of these proteins and inhibited the expression of P-gp. Conclusion:  These findings reveal that the drug resistance could be acquired through mitogen-activated protein kinase-dependent upregulation of P-gp. This mechanism protects R-HepG2 cells from the anticancer action of doxorubicin. “
“See article in J. Gastroenterol. Hepatol. 2012; 27: 566–578. For patients with advanced liver fibrosis/cirrhosis, the development of hepatocellular carcinoma (HCC) is a cause of both significant morbidity and mortality. The often late presentation of HCC, alongside patient age and comorbidity, means that radiofrequency ablation (RFA), multikinase inhibitors, and transarterial chemo-embolization frequently have a limited role.

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