Nitrotriazole AK-2123 enhances mitomycin C activity in mice bearing multidrug-resistant tumors.
The often observed cross resistance of multidrug-resistant (MDR) tumors to mitomycin C (MMC) is surprising, as these tumors are, as a rule, sensitive to alkylating drugs, and the mechanism of MMC activity is connected to alkylation of DNA. This study shows that nitrotriazole AK-2123 significantly enhances the sensitivity of MDR-strains of P388 mouse leukemia (developed and characterized by authors previously) to mitomycin C. The modulating effect is dependent on the initial sensitivity of resistant tumors to MMC which is correlated with the existence or absence of sorcin (cytosole Ca2+-binding protein) gene coamplification in MDR-amplicon. In agreement with authors' previous data about AK-2123 influence on active Ca2+-transport, it is supposed that the modulatory effect of radiosensitizer is at least partially dependent on this capacity. AK-2123 has no own antitumor effect on investigated tumors and cannot modify the sensitivity of the parent tumor P388 to MMC.
Goncharova
S A
SA
Institute of Problems of Chemical Physics, Russian Academy of Science, Chernogolovka, Moscow Region. sago@icp.ac.ru
Rajewskaya
T A
TA
Konovalova
N P
NP
Kagiya
T V
TV
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D007941:Leukemia P388 / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016685:Mitomycin / Q000627:therapeutic use*; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
D000903:Antibiotics, Antineoplastic; D011838:Radiation-Sensitizing Agents; D014230:Triazoles; C072690:AK 2123; D016685:Mitomycin