Lack of radiosensitization after paclitaxel treatment of three human carcinoma cell lines.
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.
Stromberg
J S
JS
Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073, USA.
Lee
Y J
YJ
Armour
E P
EP
Martinez
A A
AA
Corry
P M
PM
D001943:Breast Neoplasms / Q000532:radiotherapy; D002277:Carcinoma / Q000188:drug therapy / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000532:radiotherapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D008297:Male; D008938:Mitosis / Q000187:drug effects; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000532:radiotherapy; D011836:Radiation Tolerance / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011879:Radiotherapy Dosage; D014407:Tumor Cells, Cultured
D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel