Intrinsic and acquired multidrug resistance in human lung carcinomas grown in nude mice

Human epidermoid lung carcinoma xenografts with intrinsic and induced resistance were analyzed with regarding to different parameters. The xenografts with intrinsic resistance to vincristine (HXL 54) and induced drug-resistance sublines to vincristine (HXL 55/VCR), actinomycin D (HXL 55/AD) and cisplatin (HXL 55/DDP) were characterized in terms of the degree of resistance, cross-resistance, proliferation kinetics, tumorigenicity, keratin and P-glycoprotein expression. The results demonstrate that xenografts with intrinsic or induced resistance to vincristine or actinomycin D exhibit a similar general pattern of cross-resistance to that observed in multidrug-resistant cell lines. The resistance cannot be attributed to differences in proliferation kinetics. Development of resistance is associated with loss of tumorigenicity and features of differentiation, P-glycoprotein is little expressed in the resistant xenograft lines and corresponds well with the low grade of resistance.