This study aimed to evaluate the associations between ABCB1 polymorphisms G2677T/A, C3435T, and their haplotype with progression-free survival (PFS) and overall survival (OS) in 177 SCLC patients treated with cisplatin-etoposide or cyclophosphamide-epirubicin-vincristine chemotherapy.
Factors for which there is now substantial clinical evidence of a link to small cell lung cancer (SCLC) resistance to chemotherapy include MRP (for platinum-based combination chemotherapy) and MDR1/P-gp (for non-platinum agents).
Our results suggest that in H69 drug-resistant SCLC cell line TSA induces downregulation of ABCB1 expression through a transcriptional mechanism, independently of promoter methylation, and MBD1 or PCAF recruitment.
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.
Our findings suggest that the MDR1 2677G>T and 3435C>T polymorphisms can be used for predicting treatment response to etoposide-cisplatin chemotherapy in SCLC patients.
Here, we found inwardly rectifying K+ channels in a human SCLC cell line (RERF-LC-MA), which expresses no multidrug resistance-associated protein 1 (MRP1) and multidrug resistance P-glycoprotein (MDR1).
There was no correlation with SCLC sensitivity; topoisomerase IIalpha and multidrug resistance protein was expressed in all cases, lung-related multidrug resistance protein and glutathione S-transferase pie in seven of eight, and MDR1 gene in four of eight.
The following observations were made: P-glycoprotein positive (P-gp+) MDR SCLC cell line variants were lysed by human LAK cells to a greater extent than were their drug sensitive counterparts.
Combined therapy with anti-P-glycoprotein antibody and macrophage colony-stimulating factor gene transduction for multiorgan metastases of multidrug-resistant human small cell lung cancer in NK cell-depleted SCID mice.
Using a collection of small cell lung cancer (SCLC) and non-SCLC patient samples and unselected cell lines established from patients at various stages of treatment, we examined the expression of MRP2, MRP3, MRP4, and MRP5, as well as MDR1 and MRP, by PCR.
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.
The purpose of this study was to measure expression of MRP and MDR1 mRNA in cell lines and clinical samples from SCLC patients and to correlate the results with drug sensitivity profiles.
The human small cell lung cancer NCI-H69 cell line selected for resistance to etoposide (H69/VP) has been reported previously to sequentially overexpress both the MRP and MDR1 multidrug resistance-conferring genes.
A transition occurred from SCLC 74A, an intermediate form with 5% large cells to SCLC 74B, a standard mixed form with 20% of large cells, with a decrease in neuroendocrine markers and a substantial increase in P-glycoprotein, a multidrug resistance marker.
Selection for Dox resistance in SCLC may thus result in atypical multidrug-resistance characterised by absence of P-gp overexpression and atypical cross-resistance.
The present study reports that in marked contrast to H69/AR, H69/LX4 shows amplification and expression of the P-glycoprotein gene and raises the possibility that P-glycoprotein hyperexpression may be a clinically relevant component of MDR in some SCLC tumours.