[The radiosensitizer AK-2123 enhances sensitivity of MDR-tumors to Mitomycin C].
It was demonstrated that radiosensitizer AK-2123 of the triazole group significantly enhanced the sensitivity of MDR-strains of P388 murine leukemia (reported by the authors earlier) to mitomycin C (MMC). There was a direct correlation between the modulating effect of AK-2123 and dose increase from 1 to 10 mg/kg. The effect depended on the initial sensitivity of the MMC-resistant strain which in turn correlated with the absence or presence of sorcin (cytosole low-molecular Ca(2+)-binding protein) gene coamplification in the mdr-amplicon. Since AK-2123 was reported earlier by us to disrupt active Ca(2+)-transport, it is suggested that the modulating effect of the radiosensitizer was at least partially due to said disruption. AK-2123 exerted no antitumor action of its own whatsoever. It could neither modify the sensitivity of parent strain P388 to MMC, nor overcome the cross resistance of one of the MDR-tumor strains under study to such drugs as etoposide and adriablastin.
Goncharova
S A
SA
Institute for Research in Chemical Physics, Russian Academy of Sciences, Chernogolovka, Russia.
Raevskaia
T A
TA
Konovalova
N P
NP
Kagiia
V T
VT
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D007941:Leukemia P388 / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014230:Triazoles / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D014230:Triazoles; C072690:AK 2123; D016685:Mitomycin
Povyshenie chuvstvitel'nosti lekarstvenno-ustoĭchivykh opukholeĭ k mitomitsinu C s pomoshch'iu radiosensibilizatora AK-2123.