Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The P-glycoproteins (Pgps) are a small family of transport proteins associated with the multidrug resistance phenotype of cell lines selected for growth in cytotoxic drugs. Utilizing low stringency screening, we have identified a novel gene closely related to the Pgps expressed in the pig and other mammalian liver which we have called Sister of P-glycoprotein (spgp). Sequence of this gene shows it to be a member of the ATP-binding cassette family of transporters and the gene most closely related to Pgp identified to date. The function of spgp is not known, but it can be recognized by at least one Pgp mAb, C219. This cross-reactivity has implications for expression studies in tissues and tumors utilizing this and other Pgp antibodies.
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PMID:Identification of a sister gene to P-glycoprotein. 753 46

As previously reported, a novel gene P28GANK conferred a multidrug resistant phenotype in gastric cancer cells. The aim of this study was to explore the role of P28GANK in the development of multidrug resistance (MDR) in osteosarcoma cells. P28GANK gene was found to be overexpressed at the mRNA level and the protein level in a cisplatin induced MDR osteosarcoma cell line Saos-2/CDDP compared to its parent cell line Saos-2. Here, we transfected the osteosarcoma cell line Saos-2 with eukaryotic expression vector of P28GANK. In vitro drug sensitivity assay suggested that Saos-2-P28GANK cells conferred resistance to both P-glycoprotein (P-gp)-related and P-gp-nonrelated drugs. Blocking P28GANK expression in MDR osteosarcoma cells Saos-2/CDDP by P28GANK-specific small interfering RNA (siRNA) increased the cell sensitivity to various chemotherapeutic drugs. Flow cytometry examination suggested that P28GANK gene expression could suppress Adriamycin-induced apoptosis accompanied by decreased accumulation and increased release of Adriamycin. Semiquantitative RT-PCR, Western blot and Luciferase reporter assay suggested that P28GANK gene could significantly up-regulate the expression of MDR-1 and Bcl-2, transcription of the MDR-1 gene and down-regulate the expression of Bax. In addition, inhibition of P28GANK expression by RNA interference or P-gp inhibition could partially reverse P28GANK-mediated MDR. Taken together, our findings suggest that down-regulation of P28GANK gene expression could sensitize osteosarcoma cells to chemotherapeutic drugs by down-regulation of the MDR-1 and Bcl-2 and up-regulation of Bax gene expression, without altering the glutathione S-transferase activity, or intracellular glutathione content in osteosarcoma cells. Further study on biological function of P28GANK may be helpful for understanding MDR mechanism of osteosarcoma and developing a strategy for osteosarcoma treatment.
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PMID:Novel gene P28GANK confers multidrug resistance by modulating the expression of MDR-1, Bcl-2 and Bax in osteosarcoma cells. 2128 9

A leading cause of cancer chemotherapy failure is chemoresistance, which often involves multiple mechanisms. Chinese medicines (CM) usually contain multiple components which could potentially target many mechanisms simultaneously and may offer an advantage over single compounds that target one mechanism at a time. The purpose of this study was to investigate the chemosensitizing effect (CE) of a specific CM, Tripterygium wilfordii (TW), on prostate cancer cells resistant to docetaxel (Dtx) and identify the potential mechanisms. The CE of TW (in combination with Dtx) was evaluated in two Dtx resistant prostate cancer cell lines (PC3-TxR and DU145-TxR) and the efficacy of the combination for resistant PC3-TxR tumor was investigated using a xenograft mouse model. For mechanistic study, the inhibitory effect of TW on P-glycoprotein activity was assessed. In addition, novel gene targets of TW were identified using DNA microarray and quantitative PCR. Results showed that TW induced a CE of 8 and >38 folds in PC3-TxR and DU145-TxR cells, respectively with Dtx IC50 reversed back to that of the sensitive parent cells. An optimum dose of TW+Dtx significantly retarded tumor growth in mice compared to TW or Dtx alone. TW inhibited P-glycoprotein activity and induced a significant gene expression changes in genes related to angiogenesis, cell cycle regulation and differentiation. Our in vitro and in vivo studies demonstrate that TW in combination with Dtx was able to overcome the chemoresistance and suppress resistant prostate tumor growth via multi-mechanisms.
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PMID:Overcoming chemoresistance in prostate cancer with Chinese medicine Tripterygium wilfordii via multiple mechanisms. 2748 34