In Vitro Synergistic Interaction between DTA0100 and Radiation in Human Cancer Cell Lines

Abstract

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.

Inhibition of Polo-Like Kinase 1 Induces Cell Cycle Arrest and Sensitizes Glioblastoma Cells to Ionizing Radiation

“…[29][30][31][32][33] In the present study, we demonstrate that PLK1 inhibition with BI 2536 causes mitotic arrest in GBM cell lines, and that pretreatment with this drug efficiently sensitizes cells to radiation by decreasing proliferation and self-renewal in all the cell lines tested. Decreased proliferation after treatment with BI 2536 alone has already been demonstrated in different tumors: cervix adenocarcinoma, 24 leukemia, 34 anaplastic thyroid carcinoma, 35 melanomas, 15 and osteosarcoma cells.…”

In vitro targeting of Polo-like kinase 1 in bladder carcinoma

“…27 Conversely, compelling evidence has shown that combinatorial treatment with drugs that induce G 2 /M arrest could enhance the radiosensitivity of cells. 28,29 Synergistic effects on clonogenicity have been demonstrated in rectal tumor cells using PLK1 inhibition by siRNA combined with radiation, 26 this approach has also been effective on head-and-neck squamous cell carcinoma. 30 Comparatively, the pharmacological inhibition of PLK1 by BI 2536 has shown to radiosensitize medulloblastoma cells, 31 whereas GSK461364A-sensitized tumor cells to radiation and prevented the growth of metastatic breast cancer cells.…”