Goncharova S A, Raevskaia T A, Konovalova N P, Kagiia V T
Institute for Research in Chemical Physics, Russian Academy of Sciences, Chernogolovka, Russia.
Vopr Onkol. 2000;46(2):202-8.
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.
结果表明，三唑类放射增敏剂AK - 2123能显著增强P388小鼠白血病MDR菌株（作者先前报道过）对丝裂霉素C（MMC）的敏感性。AK - 2123的调节作用与剂量从1 mg/kg增加到10 mg/kg之间存在直接相关性。该作用取决于MMC耐药菌株的初始敏感性，而这又与mdr扩增子中是否存在sorcin（胞质低分子Ca(2 +)结合蛋白）基因共扩增相关。由于我们先前报道AK - 2123可破坏活性Ca(2 +)转运，因此提示放射增敏剂的调节作用至少部分归因于上述破坏。AK - 2123自身没有任何抗肿瘤作用。它既不能改变亲本菌株P388对MMC的敏感性，也不能克服所研究的一种MDR肿瘤菌株对依托泊苷和阿霉素等药物的交叉耐药性。
