alpha(2)-Macroglobulin: a novel cytochemical marker characterizing preneoplastic and neoplastic rat liver lesions negative for hitherto established cytochemical markers.
We have established McArdle-RH7777 (rat hepatoma) cell lines stably expressing mouse AADA cDNA and performed metabolic labeling as well as lipid mass analyses.
In contrast to the nonsteroidal LXR agonist N-(2,2,2-trifluoroethyl)-N-[4-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]phenyl]-benzenesulfonamide (T0901317), 3alpha, 6alpha, 24-trihydroxy-24, 24-di(trifluoromethyl)-5beta-cholane (ATI-829), a novel potent synthetic steroidal LXR agonist, was a poor inducer of sterol regulatory element-binding protein 1c expression in hepatoma HepG2 cells, whereas both compounds increased ABCA1 expression in macrophage THP-1 cells.
The results indicate that the MDR1 gene is overexpressed in liver tumors and some preneoplastic lesions and that might account for the very poor response of primary liver cancers to chemotherapy.
Inhibition of P-glycoprotein expression and reversal of drug resistance of human hepatoma HepG2 cells by multidrug resistance gene (mdr1) antisense RNA.
To evaluate the role of the MDR1 gene in the drug resistance of hepatoma, we tested nine human hepatoma cell lines for their expression of the MDR1 gene.
We tested whether the uremic toxin indoxyl sulfate (IS), an endogenous ligand of the transcription factor aryl hydrocarbon receptor, could change the expression of the following liver transporters involved in drug clearance: <i>SLC10A1</i>, <i>SLC22A1</i>, <i>SLC22A7</i>, <i>SLC47A1</i>, <i>SLCO1B1</i>, <i>SLCO1B3</i>, <i>SLCO2B1</i>, <i>ABCB1</i>, <i>ABCB11</i>, <i>ABCC2</i>, <i>ABCC3</i>, <i>ABCC4</i>, <i>ABCC6</i>, and <i>ABCG2</i> We showed that IS increases the expression and activity of the efflux transporter P-glycoprotein (P-gp) encoded by <i>ABCB1</i> in human hepatoma cells (HepG2) without modifying the expression of the other transporters.
A former study evaluated the roles of four multidrug resistance-related proteins, namely multidrug resistance protein 1 (MDR1), breast cancer resistance protein (BCRP), multidrug resistance-related protein (MRP1), and lung resistance-related protein (LRP), in the MDR mechanism of the multidrug resistant hepatoma HepG2/ADM cell line and proposed that up-regulated MDR1 and BCRP are responsible for the MDR of hepatocellular carcinoma.
Notwithstanding the differences of the investigated hepatoma cell lines in P-glycoprotein function, acetaminophen-induced toxicity was similar, possibly due to different functions of drug-metabolizing systems.
Fucoxanthin attenuates rifampin-induced cytochrome P450 3A4 (CYP3A4) and multiple drug resistance 1 (MDR1) gene expression through pregnane X receptor (PXR)-mediated pathways in human hepatoma HepG2 and colon adenocarcinoma LS174T cells.
The pro-oxidants H2O2 and buthionine sulfoximine down-regulated HIF-1alpha and P-gp, whereas up-regulation was achieved with the radical scavengers dehydroascorbate, N-acetylcysteine, and vitamin E. The correlation of HIF-1alpha and P-gp expression was validated by the use of hepatoma tumor spheroids that were either wild type (Hepa1) or mutant (Hepa1C4) for aryl hydrocarbon receptor nuclear translocator (ARNT), i.e., HIF-1beta.
There was no consistent increase or decrease in Pgp expression in secondary hepatic neoplasms compared with paired perineoplastic liver.(ABSTRACT TRUNCATED AT 250 WORDS)
Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis.
Our results demonstrate that the short-term SAM supplementation in the Mdr2-KO mice inhibited liver tumor development potentially by increasing multiple tumor suppressor mechanisms resulting in cell cycle arrest.
In the present study, we investigated: 1) ABCB6 expression in 18 resected human hepatocellular carcinoma (HCC) tissues and 3 human hepatoma cell lines; 2) pattern of ABCB6 expression during liver disease progression; and 3) functional significance of ABCB6 expression to HCC using the hepatoma cell line Huh7.