Radiosensitization by the combination of SR-2508 and paclitaxel in hypoxic human tumor cells in vitro.
The two radiosensitizers SR-2508 (etanidazole) and paclitaxel (taxol) have different dose-limiting toxicities in humans. Combination of the two radiosensitizers may increase radiosensitization without increasing toxicity. This study was carried out to determine the synergistic radiosensitizing effect of combination of SR-2508 and paclitaxel in two hypoxic human tumor cell lines: a breast carcinoma (MCF-7) and a carcinoma cervicis (HeLa). The 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to determine the number of surviving cells. Cell cycle was evaluated by flow cytometry. Cell viability was measured by the ability of single cells to form colonies in vitro. Our data demonstrated that the radiosensitization produced by the two radiosensitizers was additive in hypoxic HeLa cells while held in the G(1) phase of the cell cycle. On the other hand, there was no synergistic radiosensitizing effect in hypoxic MCF-7 cells by combination of the two drugs. Our results suggested that the synergistic radiosensitizing effect of SR-2508 and paclitaxel may be tumor-dependent and that breast cancer may not be a good candidate. This study may provide a new combination of radiosensitizers in radiotherapy for cervical carcinoma.
Jin
Cheng
C
Department of Radiation Medicine, Fourth Military Medical University, Xi'an, 710032 China.
Bai
Ling
L
Guo
Guozhen
G
D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000473:pathology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D017341:Etanidazole / Q000008:administration & dosage*; D006367:HeLa Cells; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage*; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage
D000970:Antineoplastic Agents; D011838:Radiation-Sensitizing Agents; D017341:Etanidazole; D017239:Paclitaxel