Cellular Models of Drug- and Radiation-resistant Small Cell Lung Cancer

Background: The H69-EPR, H69-CP, H69-VP and H69/R38 resistant sublines of the classic small cell lung cancer (SCLC) line have proven useful in studies of resistance and its circumvention with paclitaxel. Materials and Methods: The suppressor/oncogene profile of these sublines determined by Western and Northern blot was compared to the variant H82 SCLC cell profile. Two-dimensional electrophoresis/mass spectrometry was used to determine the effect of paclitaxel on protein expression. Results: The H69-EPR and H69-CP resistant sublines were similar to the variant H82 cells for bcl-2, p21 waf1 , p53, N-myc and c-myc expression while the H69-VP subline retained the classic H69 pattern. A 1-h treatment with 10ng/ml paclitaxel substantially reversed the resistance except for the H69/R38 subline and tended to reverse the resistance-associated changes in protein expression in the H69-EPR subline. Conclusion: Although some resistant sublines express a variant pattern of suppressor/oncogenes with low bcl-2, resistance is substantially reversed by paclitaxel treatment.