Study on the antitumor arug resistance in oral squamous carcinoma cells-Analysis of resistance mechanism and development of therapy for overcoming o the resistance-

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The aim of this study is to analyze the mechanism of antitumor drug resistance by using carcinoma cells isolated from oral squamous cell carcinoma patients without and with irradiation and/or chemotherapy and thereby to develop the therapy for overcoming of the resistance. The results obtained are as follows.1) Squamous cell carcinoma cells were isolated from fifteen patients by heterotransplantation of clinical specimens to nude mice : 10 cases from untreated primary lesions or metastasized lymph nodes, 3 cases from primary lesions or metastasized lymph nodes after irradiation, 2 cases from recurrent lesions after irradiation and chemotherapy. Each tumor showed a different sensitivity to bleomycin, but most of the tumors isolated after irradiation and chemotherapy showed a low sensitivity to antitumor agents.2) Five cases in 15 cases (32 specimens) of clinical materials and 2 cases in 6 cases of cultured tumor cells showed a positive staining forP-glycoprotein, a multidrug resistance gene product, in immuno-histochemical staining with monoclonal antibody, C219.However, , protein bands by Western blotting were out demonstrated in any case.3) The CDDP-resistant KB carcinoma cells isolated in vitro (25-fold degree of resistance) were over two-fold less sensitive kto CBDCA,BLM,MMC and 5-FU,Although there was no difference in intracellular glutathione concentration between this resistant cells and KB cells, resistant cells showed only one third of the intracellular CDDP concentration and elevated expression of HSP 27 and 70, stress proteins, by immunostaining and Western blotting, as compared to KB cells.4) Antitumor effect of combination chemotherapy with THP-ADM,CDDP and 5-FU was examined using nude mouse tumors including multidrug resistant celsl. As a results, THP-ADM,5-FU and CDDP was more effective than THP-ADM,CDDP and 5-FU in the sequence of administration. The combination with synthetic isoprenoid increased the effect of BLM.