Revista de carcinogénesis y mutagénesis

Abstracto

Radio sensitization of Colon Cancer Cells Mediated by Gemcitabine through Cell Cycle Synchronization

Zanandrea M, Baes TW, Leon LB, Amado GV, Reis VS, Filho AB, Rocha AB and Grivicich I

We evaluated gemcitabine together with ionizing radiation for improved cell growth inhibition with respect to that by radiation alone in the human colon carcinoma cell lines SW620, HT-29 and SNU-C4. To this end, cells were exposed for 24 h to gemcitabine and then assessed for growth response with the sulphorhodamine B assay. The cell lines, as well as exposed to ionizing radiation and a combination of gemcitabine and ionizing radiation for 24 h, 48 h and 72 h and the radiosensitivity was assessed using a clonogenic assay. Multiple drug effect analysis was used to evaluate the synergistic effect, which was then related to the cell cycle phase distribution. The SNU-C4 cell line showed a greater sensitivity to gemcitabine in comparison to the other two cell lines, while the SW620 cells was more sensitive to damage induced by radiation. Furthermore, gemcitabine increased by 50% the effect of ionizing radiation after 24 h in SW620 cell line, while in the others cell lines, this effect was observed only after 72 h. Moreover, gemcitabine associated with ionizing radiation was synergistic in SW620, HT-29 and SNU-C4 cells. Increased in S phase fraction was seen in gemcitabine treatment in all cell lines studied. While, ionizing radiation only induced an accumulation on G2/M in SW620 and HT-29 cell lines, indicating that SNU-C4 is less sensitive to radiation effect. A significant accumulation of cells in S phase after treatment with gemcitabine followed by radiation was observed in all cell lines. In summary our data indicate that gemcitabine increases the radiosensitivity to radiation in cell lines derived from human colon cancer, and that this effect seems to be associated with the ability of gemcitabine to synchronize cells in S phase of the cell cycle.