Zidovudine Induces Alterations of Apoptosis and Resistance to Antineoplastic Agents in T-Cell Lymphoma Cells

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• 作者：Kotchetkov ; R. ; Grö ; schel ; B. ; Cinatl ; J. ; Kornhuber ; B. ; Rabenau ; H. ; Cinatl Jr ; J.
• 刊名：Antiviral Research
• 出版年：1997
• 出版时间：April, 1997
• 年：1997
• 卷：34
• 期：2
• 页码：A60
• 全文大小：101 K

文摘

Prolonged treatment of leukemic cell lines with antiretroviral agents such as nucleoside analogues may result in the development of cell resistance against antiviral agents. We tested whether prolonged treatment of H9 cells (T-cell lymphoma cell line) with 3′-azido-3′-deoxythymidine (AZT) interferes with the sensitivity to antitumor agents commonly used for treatment of AIDS-associated lymphomas H9 cells grown for more than two years in medium containing 250 μM of AZT were at least 100-fold less sensitive to cytotoxic effects of AZT than parental H9 cell line. These cells designated H9^tAZT²⁶⁰ were 5- to 20-fold less sensitive to toxic effects of antitumor agents including cisplatin (CP), vincristine (VIN), doxorubicin (DOX) and etoposide (VP-16). The resistance to antitumor agents was associated with inhibition of apoptosis as demonstrated by the terminal deoxynucleotidyl transferase-mediated nicked-end labeling (TUNEL) assay and DNA fragmentation assay. The regulation of genes involved in the regulation of apoptosis such as bel-2 was changed in H9^tAZT cells. The results demonstrate that prolonged treatment of tumor cells with AZT may result in the development of resistance to antineoplastic agents due to the alterations in apoptosis.