BioLab, Instituto Universitario de Bio-Organica Antonio Gonzalez, Universidad de La Laguna, C/ Astrofisico Francisco Sanchez 2, 38206 La Laguna, Spain.
Anticancer Agents Med Chem. 2012 Oct 1;12(8):988-93. doi: 10.2174/187152012802650057.
DTA0100 is a new catalytic inhibitor of the human DNA topoisomerase IIα that induces G2/M phase cell cycle arrest in human solid tumor cells lines from various malignancies. In our study, we investigated the effectiveness of the combined treatment of ionizing radiation with DTA0100 on the survival of three representative human solid tumor cell lines: HeLa (cervix), WiDr (colon) and SW1573 (non-small cell lung cancer). The concomitant treatment of DTA0100 and irradiation showed a synergistic and antagonistic effect in the three cell lines tested. A synergistic cytotoxic effect of the combination of DTA0100 and radiation was confirmed by the median drug effect analysis method. It was found that in those protocols where the drug was administered after radiation the most synergistic effect was achieved. Our study constitutes the first in vitro evidence for synergistic effects between DTA0100 and radiation. This combination therapy might thus be expected to be more effective than either treatment alone in patients with cervical, colon and non-small cell lung cancer cells.
DTA0100 是一种新型的人类 DNA 拓扑异构酶 IIα 的催化抑制剂，可诱导多种恶性肿瘤的人类实体瘤细胞系停滞在 G2/M 期。在我们的研究中，我们研究了电离辐射与 DTA0100 联合治疗对三种代表性的人类实体瘤细胞系（HeLa[宫颈]、WiDr[结肠]和 SW1573[非小细胞肺癌]）存活的影响。在三种测试的细胞系中，DTA0100 和辐照的同时处理显示出协同和拮抗作用。通过中值药物效应分析方法证实了 DTA0100 和辐射联合的协同细胞毒性作用。结果发现，在药物在辐射后给予的那些方案中，达到了最协同的效果。我们的研究构成了 DTA0100 和辐射之间协同作用的第一个体外证据。因此，与单独治疗相比，这种联合治疗可能对患有宫颈癌、结肠癌和非小细胞肺癌的患者更有效。
