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.
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Authors | Y Abe, Y Ohnishi, M Yoshimura, E Ota, Y Ozeki, Y Oshika, T Tokunaga, H Yamazaki, Y Ueyema, T Ogata, N Tamaoki, M Nakamura |
Journal | British journal of cancer
(Br J Cancer)
Vol. 74
Issue 12
Pg. 1929-34
(Dec 1996)
ISSN: 0007-0920 [Print] England |
PMID | 8980392
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
- Antigens, Neoplasm
- DNA-Binding Proteins
- Isoenzymes
- Vincristine
- Glutathione Transferase
- DNA Topoisomerases, Type II
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Topics |
- ATP Binding Cassette Transporter, Subfamily B, Member 1
(biosynthesis)
- Animals
- Antigens, Neoplasm
- DNA Topoisomerases, Type II
(metabolism)
- DNA-Binding Proteins
- Drug Resistance, Multiple
(physiology)
- Gene Expression Regulation, Neoplastic
- Genes, MDR
(genetics)
- Glutathione Transferase
(metabolism)
- Humans
- Isoenzymes
(metabolism)
- Lung Neoplasms
(physiopathology)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Tumor Cells, Cultured
- Vincristine
(administration & dosage)
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