Establishment of tumor cell lines from a patient with head and neck cancer and their different sensitivities to anti-cancer agents

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Abstract
The authors established five cell lines from a human head and neck tumor. The five cell lines (HC-2, HC-3, HC-4, HC-7, and HC-9) exhibited different sensitivities to Adriamycin, cisplatin, bleomycin, 5-fluorouracil, vincristine, and daunomycin. The D50 was 200 ng/ml Adriamycin (doxorubicin) for HC-7 and 45 ng/ml for HC-2. At the inception of long-term culture (11 months) in the absence of any drug, the sensitivity to Adriamycin of HC-7-5 (subcloned from HC-7) was 3.4 times greater than that of HC-2-6 (subcloned from HC-2); by 11 months, it decreased to 1.6 times that of HC-2-6. The cytocidal action of Adriamycin on HC-2-6 and HC-7-5 was potentiated when Adriamycin was combined with verapamil or cepharanthine. Cepharanthine also potentiated daunomycin and vincristine (VCR) against HC-2-6 and HC-7-5 cells, and it almost completely overcame drug-resistance to daunomycin and vincristine in HC-7-5/VCR, a multidrug-resistant variant isolated after long exposure to vincristine of HC-7-5 cells in culture. The cellular accumulation of [3H]-daunomycin by HC-7-5 cells was about 70% that of HC-2-6 cells. By Northern blot analysis, using a multidrug-resistance gene (mdr-1) probe, neither HC-2-6 nor HC-7-5 expressed the mdr-1 gene, but HC-7-5/VCR or other multidrug-resistant variants showed active expression of the mdr-1 gene. Differential sensitivities among the five cell lines to 5-fluorouracil, cisplatinum, and bleomycin appear to be mediated through other mechanism beside the mdr-1 gene.