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P-glycoprotein-mediated acquired multidrug resistance of human lung cancer cells in vivo
- Source :
- British Journal of Cancer
- Publication Year :
- 1996
-
Abstract
- 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. Images Figure 3 Figure 4 Figure 5
- Subjects :
- Cancer Research
Pathology
medicine.medical_specialty
Vincristine
Lung Neoplasms
Mice, Nude
Mice
In vivo
Antigens, Neoplasm
Gene expression
medicine
Tumor Cells, Cultured
Animals
Humans
ATP Binding Cassette Transporter, Subfamily B, Member 1
Lung cancer
P-glycoprotein
Glutathione Transferase
Mice, Inbred BALB C
biology
Cancer
medicine.disease
Molecular biology
Drug Resistance, Multiple
Multiple drug resistance
DNA-Binding Proteins
Gene Expression Regulation, Neoplastic
Isoenzymes
DNA Topoisomerases, Type II
Oncology
biology.protein
Adenocarcinoma
Genes, MDR
medicine.drug
Research Article
Subjects
Details
- ISSN :
- 00070920
- Volume :
- 74
- Issue :
- 12
- Database :
- OpenAIRE
- Journal :
- British journal of cancer
- Accession number :
- edsair.doi.dedup.....0cc2ae90929085920d15b7a79348b286