Cancer Res Treat.  2005 Jun;37(3):191-195.

Enhancement of Radiation Effects by Flavopiridol in Uterine Cervix Cancer Cells

• Kim S
• Wu HG
• Shin JH
• Park HJ
• Kim IA
• Kim IH

Abstract

PURPOSE
To determine the effects of combinations of radiation and flavopiridol, an inhibitor of cyclin-dependent kinases and global transcription, in a human uterine cervix cancer cell line. MATERIALS AND METHODS: Human uterine cervix cancer cells (HeLa), cultured to the mid-log phase, were exposed to X-rays, flavopiridol, and combinations of X-rays and flavopiridol in various sequences. The end point in this study was the clonogenic survival, which was measured via clonogenic assays. In order to determine the intrinsic cytotoxicity of flavopiridol, 0, 5, 12.5, 25, 37.5, 50 and 100 nM of flavopiridol were added to cell culture media. In the combination treatment, four different schedules of flavopiridol and irradiation combinations were tested: treatment of flavopiridol for 24 hours followed by irradiation, simultaneous administration of flavopiridol and irradiation, and irradiation followed by flavopiridol (for 24 hours) at intervals of 6 and 24 hours. The fraction of cells surviving after the combination treatment with 2 Gy of radiation (SF2) was compared with that of the fraction of cells surviving after treatment with irradiation alone. RESULTS: The cytotoxicity of flavopiridol was found to be dose-dependent, with an IC50 of 80 nM. No cytotoxic enhancements were observed when flavopiridol and radiation were administered simultaneously. Flavopiridol, administered either 24 hours before or 6 hours after irradiation, exerted no sensitizing effects on the cells. Only one protocol resulted in a radiosensitizing effect: the administration of flavopiridol 24 hours after irradiation. CONCLUSION: Flavopiridol enhanced the effects of radiation on a uterine cervix cancer cell line in vitro, and this enhancement was both sequence- and time-dependent.

Keyword

Flavopiridol; Radiation; Uterine cervix cancer

MeSH Terms

Appointments and Schedules
Cell Culture Techniques
Cell Line
Cervix Uteri*
Cyclin-Dependent Kinases
Female
Humans
Inhibitory Concentration 50
Radiation Effects*
Radiation-Sensitizing Agents
Cyclin-Dependent Kinases
Radiation-Sensitizing Agents

Figure

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  Fig. 1 Cytotoxicity of flavopiridol at nanomolar concentrations. Filled circles represent the experimental data, and the dotted line is a regression line.

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  Fig. 2 Surviving fraction of HeLa cells after simultaneous flavopiridol and irradiation treatment, compared with that of cells treated with irradiation alone. Error bars represent standard errors.

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  Fig. 3 Surviving fraction of HeLa cells after sequential treatment with flavopiridol and irradiation compared with that of cells treated with irradiation alone. (A) Flavopiridol followed by irradiation after a 24-hour interval, (B) Irradiation followed by flavopiridol after a 6-hour interval, (C) Irradiation followed by flavopiridol after a 24-hour interval. Error bars represent standard errors.

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