These results indicate that the multidrug resistance phenotype in human hepatocellular carcinoma cells cannot be attributed to expression of the MDR1 gene, but that novel mechanisms may account for the resistance of these cancer cells.
Staining of P-glycoprotein with the C-219 antibody is technically simple and is useful for studying the role of P-glycoprotein in drug-resistant hepatocellular carcinoma.
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 characterized Pgp expression in the HCC lines Hep3B, Hep G2, and SK-HEP-1 by immunohistochemistry and the reverse transcription-polymerase chain reaction.
Immunohistochemical study of the biopsy or resected hepatocellular carcinoma specimens was performed using the avidin-biotin-peroxidase technique with monoclonal antibody JSB-1 directed against P-glycoprotein.
Inhibition of P-glycoprotein expression and reversal of drug resistance of human hepatoma HepG2 cells by multidrug resistance gene (mdr1) antisense RNA.
This study suggested that the measurement of the MDR-1 mRNA levels in HCC and nontumorous liver tissue might be a useful prognostic factor after surgical resection in patients with HCC.
The multidrug resistance (MDR) transporters MDR1-P-glycoprotein and MRP2 (multidrug-associated protein 2) are expressed in almost 50% of human cancers, including HCCs.
Fusion of the EGFP significantly triggers tumorigenic VEGF signalling in three E3-, F11- and A(3-1)-transfected human HCC cell lines, compared with the parental EGFP-free malignant hepatocellular carcinoma (MHCC)1 cell line; Redox-regulated VEGF upstream mechanism interplays dramatically mediate dual responses, either down- or upregulating tumorigenic VEGF signalling, which depends on individual post-transcriptional regulation or upstream modification of the VEGF promoter in the three MHCC1, SMCC7721 and doxorubicin-resistance 7402/D+ non-transfected human HCC cell lines; and mechanism-based strategies for stimulating beta-adrenergic and P2-purinergic signal transduction and counteracting O2 and Ca2+-inflow significantly trigger tumorigenic VEGF signalling in ATRA/ATRP-driven networks, compared with controls of the non-transfected cell types examined.
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.
We developed an anti-MDR1 hammerhead ribozyme and delivered it to P-gp-overproducing human hepatocarcinoma cell line HepG2 by a retroviral vector containing RNA polymerase III promoter.
Expression of multiple drug resistant (MDR) phenotype and over-expression of P-glycoprotein (P-gp) in the human hepatocellular carcinoma (HCC) cell clone P1(0.5), derived from the PLC/PRF/5 cell line (P5), are associated with strong resistance to oxidative stress and a significant (p < 0.01) increase in intracellular vitamin E content as compared with the parental cell line.
Expression of P-gps (multidrug export pump MDR1 (ABCB1), phospholipid flippase MDR3 (ABCB4), sister of P-glycoprotein SPGP (ABCB11)) and basolateral MRP homologue MRP3 (ABCC3) showed a trend for decreased levels in HCC but was highly variable among individual tumors.