Multidrug resistance in small cell lung cancer: expression of P-glycoprotein, multidrug resistance protein 1 and lung resistance protein in chemo-naive patients and in relapsed disease.
The aim of this study was to investigate the expression of multidrug resistance-associated proteins in metastatic small cell lung cancer (SCLC) cells correlated to cisplatin/etoposide chemotherapy response and the level of those proteins in relapsed disease. Samples were obtained by transbronchial fine needle aspiration biopsy (TBNA) of enlarged mediastinal lymph nodes in 17 patients. After cytological confirmation of SCLC, cells were stained by a panel of mAbs against internal epitopes of P-gp (JSB-1), MRP1 (MRPr1), LRP (LRP-56) and cytokeratin (MNF116) and analyzed by flow cytometry. We observed a significant negative correlation for better response rate to chemotherapy with individual expression of P-gp (r=-0.93, P<0.0001; Pearson correlation) and MRP1 (r=-0.78, P=0.0002; Pearson correlation) in chemo-naive SCLC cells and a non-significant correlation for LRP expression. P-gp and MRP1 expression was markedly increased in metastatic cells in four out of five patients with relapsed disease (4-12 months after starting chemotherapy), in comparison to their chemo-naive values. In conclusion, the results suggest that P-gp and MRP1 might be associated with SCLC cell survival during metastasis and chemotherapy, and that overexpression of those transporters in relapsed disease could assist short-term chemotherapy efficiency.
Triller
Nadja
N
University Clinic of Respiratory and Allergic Diseases, 4204 Golnik, Slovenia. nadja.triller@klinika-golnik.si
Korosec
Peter
P
Kern
Izidor
I
Kosnik
Mitja
M
Debeljak
Andrej
A
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism*; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D002945:Cisplatin / Q000627:therapeutic use; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism; D011446:Prospective Studies; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D000099187:Major Vault Protein
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002945:Cisplatin; D005047:Etoposide; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein