This underscores the need for combinatorial approaches with focus on PXR antagonism to improve drug effectiveness in hepatocellular carcinoma.<b>Abbreviations:</b> HCC: Hepatocellular Carcinoma; FDA: Food and Drug Administration; TGF-β: Transforming growth factor-β; PXR: Pregnane X receptor; CAR: Constitutive androstane receptor; P-gp/ABCB1: P-glycoproteins/ATP-binding cassette transporter subfamily B member 1; MRP1/ABCC1 and MRP2/ABCC2: Multidrug-resistance associated proteins; BCRP/ABCG2: Breast cancer resistant protein; DMEs: Drug-metabolizing enzymes; CFDA: 5,6-carboxyfluorescein diacetate; ETS1: Transcription factor E26 transformation specific sequence 1.
MDR1 gene polymorphism correlated with pathological characteristics and prognosis in patients with primary hepatocellular carcinoma receiving interventional therapy.
Here we tested the P-gp interaction of some A<sub>3</sub> adenosine receptor agonists that are being developed for the treatment of chronic diseases, including rheumatoid arthritis, psoriasis, chronic pain, and hepatocellular carcinoma.
Repression of RNA pol III-dependent transcription by chemical inhibition or knockdown of BRF1 RNA pol III transcription initiation factor subunit (BRF1) enhanced HCC cell sensitivity to doxorubicin, suggesting that MAF1 regulates doxorubicin resistance in HCC by controlling RNA pol III-dependent transcription.
These findings establish a novel miRNA-based approach for autophagy interference to reverse doxorubicin resistance in future chemotherapy regimens against human HCC.
N-Acetyltransferase 10 Enhances Doxorubicin Resistance in Human Hepatocellular Carcinoma Cell Lines by Promoting the Epithelial-to-Mesenchymal Transition.
Consequently, P-gp will play an important role in the disposition of cinobufotalin <i>in vivo</i>, which provided a new combination therapy for the clinical treatment of HCC.
These data indicate that the miR-338-5p/EGFR/ABCB1 regulatory loop plays a critical role in HCC, and a negative correlation between miR-338-5p and EGFR or ABCB1 was also detected in HCC clinical samples.
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.
P-glycoprotein or membrane pump induced drug efflux and altered prosurvival Bcl-2 expression are key mechanisms for drug resistance leading to failure of chemotherapy in HCC.
Using in vitro assays, we show that repeated miRNA treatments resulted in gradual reduction of HCC cell proliferation and reversal of doxorubicin resistance.
Previous researches indicated that cyclooxygenase-2 (Cox-2) might be involved in P-glycoprotein (P-gp)-mediated multidrug resistance in hepatocellular carcinoma cells.
Multidrug resistance (MDR) due to overexpression of P-glycoprotein (P-gp) is a major obstacle that hinders the treatment of hepatocellular carcinoma (HCC).