Multidrug-resistant gene expression in small-cell lung cancer.
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.
Savaraj
N
N
Section of Hematology/Oncology, V.A. Medical Center, Miami, FL 33125, USA.
Wu
C J
CJ
Xu
R
R
Lampidis
T
T
Lai
S
S
Donnelly
E
E
Solomon
J
J
Feun
L G
LG
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015152:Blotting, Northern; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D015996:Survival Rate; D014158:Transcription, Genetic; D017211:Treatment Failure; D014407:Tumor Cells, Cultured; D014750:Vincristine / Q000008:administration & dosage
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D002945:Cisplatin