[Increasing chemosensitivity to cisplatin by glutathione depletion with buthionine sulfoximine. In vitro and in vivo studies with a human squamous cell cancer line].
The success of antineoplastic chemotherapy in head and neck carcinoma is limited by the insufficient primary chemosensitivity of the tumor and/or the decrease of drug efficacy in the course of treatment. As regards cisplatin (CDDP) this phenomenon of chemoresistance may be closely associated with glutathione (GSH) metabolism since GSH is responsible for the detoxication of active CDDP hydrolysates. In the human squamous carcinoma cell line HLac 79, selective inhibition of GSH synthesis by buthionine sulfoximine (BSO) led to enhanced CDDP chemosensitivity both in vitro and in vivo. Using the colony-forming assay GSH depletion of HLac 79 tumor cells of more than 90% (Table 1) resulted in a dose modifying factor of 2 (Table 2). Combined treatment of HLac 79 tumor-bearing nude mice with BSO and CDDP brought about significant increase in mean survival time (p less than 0.001) as compared to the CDDP-treated group. The possible role of BSO as chemosensitizer is discussed.
Bier
H
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HNO-Klinik am Klinikum Mannheim, Universität Heidelberg.
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000633:toxicity; D019328:Buthionine Sulfoximine; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology* / Q000633:toxicity; D003114:Colony-Forming Units Assay; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007822:Laryngeal Neoplasms / Q000473:pathology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000964:Antimetabolites, Antineoplastic; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; D002945:Cisplatin
Erhöhung der Chemosensitivität gegenüber Cisplatin durch Glutathion-Depletion mit Buthionin Sulfoximin. In-vitro- und In-vivo-Untersuchungen an einer humanen Plattenepithelkarzinomlinie.