The effect of p53-function on the sensitivity to paclitaxel with or without hyperthermia in human colorectal carcinoma cells.
The importance of p53-function for the sensitivity to paclitaxel with and without hyperthermia (HT) was studied in an isogenic cell line system. The inactivation of p53 decreased sensitivity to paclitaxel (1.1-2.5-fold), which correlated with a lower induction of apoptosis. The magnitude of the G2/M arrest after treatment with paclitaxel was similar in all cell lines. The cytotoxicity of paclitaxel was not enhanced by HT in either wild-type p53 or p53-inactivated cells. In conclusion, cellular sensitivity to paclitaxel depends on p53-function by its ability to induce apoptosis. Irrespective of the p53-function HT was not able to enhance the sensitivity to paclitaxel.
van Bree
C
C
Department of Radiotherapy, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands.
Savonije
J H
JH
Franken
N A
NA
Haveman
J
J
Bakker
P J
PJ
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006358:Hot Temperature; D006801:Humans; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D000972:Antineoplastic Agents, Phytogenic; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel