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Lack of radiosensitization after paclitaxel treatment of three human carcinoma cell lines
Author(s) -
Stromberg Jannifer S.,
Lee Yong J.,
Armour Elwood P.,
Martinez Alvaro A.,
Corry Peter M.
Publication year - 1995
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19950501)75:9<2262::aid-cncr2820750912>3.0.co;2-5
Subject(s) - paclitaxel , medicine , clonogenic assay , cell cycle , flow cytometry , radiation therapy , cell culture , cytotoxicity , cell , cancer research , oncology , chemotherapy , cancer , immunology , in vitro , biology , biochemistry , genetics
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.