Abstract
The development of drug resistance can contribute to treatment failure in small-cell lung cancer (SCLC). In this report, we investigate p-glycoprotein-mediated multidrug resistance (MDR) in these patients. Tumor tissue was obtained prior to treatment and at relapse if possible, short-term culture was carried out, and these tumor cells were analyzed for MDR gene expression by slot blot and reverse transcriptase polymerase chain reaction (RT-PCR) and northern blot analysis. Three cell lines were also established from short-term cultures. Twenty-four patients with MDR(-) and seven with MDR +(++) were available for survival analysis. Median survival for MDR (-) patients was 10 months, whereas for MDR +(++) patients it was 2 months. This was statistically significance (p < 0.0007). The presence of MDR1 gene expression also correlated with the lack of response to chemotherapy (p < 0.001). Increased MDR1 gene expression is usually present in patients with more tumor burden at initial diagnosis. Furthermore, loss of MDR1 gene expression can occur in intrinsically MDR(+) SCLC cells after multiple passages in drug-free media. We concluded that increased MDR1 gene expression is present in a small number of SCLC both before and after chemotherapy and usually signifies poor survival and no response to chemotherapy.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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Adult
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Aged
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Antibiotics, Antineoplastic / administration & dosage
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents, Alkylating / administration & dosage
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Antineoplastic Agents, Phytogenic / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Blotting, Northern
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Carcinoma, Small Cell / drug therapy
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Carcinoma, Small Cell / genetics*
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Carcinoma, Small Cell / pathology
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Cisplatin / administration & dosage
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Cyclophosphamide / administration & dosage
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Doxorubicin / administration & dosage
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Drug Resistance, Neoplasm / genetics*
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Etoposide / administration & dosage
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Female
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Gene Expression Regulation, Neoplastic*
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Genes, MDR / genetics*
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Humans
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Immunoblotting
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Lung Neoplasms / drug therapy
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Lung Neoplasms / genetics*
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Lung Neoplasms / pathology
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Male
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Middle Aged
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Neoplasm Recurrence, Local / genetics
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Neoplasm Recurrence, Local / pathology
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Polymerase Chain Reaction
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Survival Analysis
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Survival Rate
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Transcription, Genetic
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Treatment Failure
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Tumor Cells, Cultured
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Vincristine / administration & dosage
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Antibiotics, Antineoplastic
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Antineoplastic Agents
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Antineoplastic Agents, Alkylating
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Antineoplastic Agents, Phytogenic
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Vincristine
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Etoposide
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Doxorubicin
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Cyclophosphamide
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Cisplatin