Intrinsic drug resistance in a human lung carcinoma xenograft is associated with overexpression of multidrug-resistance DNA-sequences and of plasma membrane glycoproteins.
The purpose of this study was to examine whether multidrug resistance can be detected in human lung tumors not previously treated with chemotherapy. Therefore, the intrinsic sensitivity or resistance of 8 human epidermoid lung cancer xenografts grown in nude mice has been examined. The tumor lines responded differently to vincristine and the other cytostatic agents. When the effects of vincristine on the 8 tumor lines are correlated with the effect of dactinomycin (actinomycin D), a close relationship could be found (r = 0.96). These results demonstrate that xenografts derived from human lung tumors not previously treated with chemotherapy exhibited a similar pattern of cross-resistance as is observed in sublines of murine and human tumors which were resistant to various drugs following repeated exposure of the cells to a sublethal concentration of these drugs. The resistant lung tumor HXL 54 also shows an overexpression of the P170-membrane glycoprotein (detected by Mab 265/F4). To determine whether multidrug genes were expressed in resistant lung tumors, slot blots and Northern blots were performed using the probes pDR 7.8 and pcDR 1.5. The level of expression can be correlated with the degree of drug resistance.
Volm
M
M
Institute of Experimental Pathology, German Cancer Research Center, Heidelberg, Fed. Rep. of Germany.
Bak
M
M
Mattern
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015152:Blotting, Northern; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002460:Cell Line; D004273:DNA, Neoplasm / Q000235:genetics*; D003609:Dactinomycin / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014750:Vincristine / Q000627:therapeutic use
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D003609:Dactinomycin; D014750:Vincristine; D004317:Doxorubicin