Lack of radiosensitization after paclitaxel treatment of three human carcinoma cell lines

Autor: Peter M. Corry, Elwood P. Armour, Alvaro Martinez, Jannifer S. Stromberg, Yong J. Lee
Rok vydání: 1995
Předmět:
Zdroj: Cancer. 75:2262-2268
ISSN: 1097-0142
0008-543X
Popis: Background. Several recent studies have suggested radiosensitizing effects of paclitaxel, a microtubular inhibitor. To test the universality of this finding, the interaction between paclitaxel and radiation treatment of cell lines derived from three common human carcinomas MCF-7 (breast cancer) ; DUT-145 (prostate cancer) ; and HT-29 (colon cancer) was evaluated. The study focused on the ability of paclitaxel to block cells at the G2-M phase of the cell cycle and potentially enhance the radiation sensitivity of the cells. Methods. All cell lines were exposed to three different clinically achievable paclitaxel concentrations ranging from 2 nM to 25 nM. Paclitaxel pretreatment for 12 and 24 hours before radiation was tested in all three cell lines. The radiation dose ranged from 0 to 8 Gy delivered in a single fraction. Cellular survival after treatment with paclitaxel and/or radiation was determined by clonogenic assay. Cell cycle distribution as determined by flow cytometry was performed after various dose-time combinations of paclitaxel. Results. Cytotoxicity studies with paclitaxel alone demonstrated a time-dependent and dose-dependent survival relationship for all three cell lines. Resultant surviving fractions were in the range of 5 to 90% after 24-hour exposure to paclitaxel alone. The interaction between paclitaxel and radiation was primarily additive in each of the three cell lines for all paclitaxel dose-time combinations studied. Flow cytometric analysis failed to reveal a prominent G2-M block in all three cell lines after paclitaxel treatment for 24 hours. Conclusions. Paclitaxel lacked a radiosensitizing effect on MCF-7, DUT-145, and HT-29 cells in this study. These results should be considered when designing clinical trials that use paclitaxel as a potential radiosensitizer of certain human carcinomas. Cancer 1995 ; 75 :2262-8.
Databáze: OpenAIRE
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