P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo. 1996

Y Abe, and Y Ohnishi, and M Yoshimura, and E Ota, and Y Ozeki, and Y Oshika, and T Tokunaga, and H Yamazaki, and Y Ueyema, and T Ogata, and N Tamaoki, and M Nakamura
Department of Pathology, Tokai University School of Medicine, Kanagawa, Japan.

We examined whether the increased expression of P-glycoprotein (P-gp) encoded by the human multidrug resistance gene MDR1 is related to the acquired multidrug resistance of lung cancer in vivo. We estimated the chemosensitivity of lung cancer xenografts (LC-6, adenocarcinoma; Lu-24, small-cell cancer) by calculation of relative tumour growth (T/C%, treated/control) in vivo, based on statistical significance determined by the Mann-Whitney U test (P < 0.01, one-sided). MDR1 gene expression levels were evaluated by reverse transcription-polymerase chain reaction (RT-PCR) assay. P-gp production and P-gp localisation were examined by Western blotting and by immunohistochemical analysis respectively. LC-6 and Lu-24 were initially sensitive to both vincristine (VCR, 1.6 mg kg-1: LC-6, 45%; Lu-24, 39%) and doxorubicin (DOX, 12 mg kg-1: LC-6, 26%; Lu-24, 27%) in vivo. VCR-resistant variants (LC-6R, 66% and Lu-24R, 68%) selected with VCR (0.4 mg kg-1, x 9) significantly acquired cross-resistance to DOX (LC-6R, 55% and Lu-24R, 55% respectively). RT-PCR assay showed increased levels of MDR1 expression in LC-6R and Lu-24R with stable MDR1 expression levels. P-gp expression levels were elevated, and the percentage of P-gp-positive tumour cells increased in both LC-6R and Lu-24R. These results suggest that P-gp/MDR1 overexpression is related to acquired multidrug resistance in lung cancer in vivo.

UI MeSH Term Description Entries
D007527 Isoenzymes Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics. Alloenzyme,Allozyme,Isoenzyme,Isozyme,Isozymes,Alloenzymes,Allozymes
D008175 Lung Neoplasms Tumors or cancer of the LUNG. Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008819 Mice, Nude Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses. Athymic Mice,Mice, Athymic,Nude Mice,Mouse, Athymic,Mouse, Nude,Athymic Mouse,Nude Mouse
D004250 DNA Topoisomerases, Type II DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex. DNA Topoisomerase (ATP-Hydrolysing),DNA Topoisomerase II,DNA Topoisomerase II alpha,DNA Topoisomerase II beta,DNA Type 2 Topoisomerase,TOP2A Protein,TOP2B Protein,Topoisomerase II,Topoisomerase II alpha,Topoisomerase II beta,Type II DNA Topoisomerase,alpha, Topoisomerase II,beta, Topoisomerase II
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D005982 Glutathione Transferase A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite. Glutathione S-Alkyltransferase,Glutathione S-Aryltransferase,Glutathione S-Epoxidetransferase,Ligandins,S-Hydroxyalkyl Glutathione Lyase,Glutathione Organic Nitrate Ester Reductase,Glutathione S-Transferase,Glutathione S-Transferase 3,Glutathione S-Transferase A,Glutathione S-Transferase B,Glutathione S-Transferase C,Glutathione S-Transferase III,Glutathione S-Transferase P,Glutathione Transferase E,Glutathione Transferase mu,Glutathione Transferases,Heme Transfer Protein,Ligandin,Yb-Glutathione-S-Transferase,Glutathione Lyase, S-Hydroxyalkyl,Glutathione S Alkyltransferase,Glutathione S Aryltransferase,Glutathione S Epoxidetransferase,Glutathione S Transferase,Glutathione S Transferase 3,Glutathione S Transferase A,Glutathione S Transferase B,Glutathione S Transferase C,Glutathione S Transferase III,Glutathione S Transferase P,Lyase, S-Hydroxyalkyl Glutathione,P, Glutathione S-Transferase,Protein, Heme Transfer,S Hydroxyalkyl Glutathione Lyase,S-Alkyltransferase, Glutathione,S-Aryltransferase, Glutathione,S-Epoxidetransferase, Glutathione,S-Transferase 3, Glutathione,S-Transferase A, Glutathione,S-Transferase B, Glutathione,S-Transferase C, Glutathione,S-Transferase III, Glutathione,S-Transferase P, Glutathione,S-Transferase, Glutathione,Transfer Protein, Heme,Transferase E, Glutathione,Transferase mu, Glutathione,Transferase, Glutathione,Transferases, Glutathione
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000951 Antigens, Neoplasm Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin. Neoplasm Antigens,Tumor Antigen,Tumor Antigens,Antigen, Tumor,Antigens, Tumor

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