The interaction of taxol and vinblastine with radiation induction of p53 and p21 WAF1/CIP1.
The combination of the microtubule active drug taxol with radiation has shown promise for use in combined modality therapy. Recent studies have demonstrated that radiation and a wide range of chemotherapy agents, including microtubule active drugs, induce p53. In certain circumstances, the induction of p53 has been shown to be an important parameter in the response of a tumour to cytotoxic treatment. We examined the induction of p53 and its downstream target, p21WAF1/CIP1, by the microtubule active agents taxol and vinblastine with radiation. An increase in induction of both p53 and p21 WAF1/CIP1 was demonstrated when radiation was added to either taxol or vinblastine treatment. These results, in conjunction with data on taxol and vinblastine induction of p21WAF1/CIP1, suggest a rationale for the combination therapy.
Tishler
R B
RB
Joint Center for Radiation Therapy, Boston, MA 02215, USA.
Lamppu
D M
DM
D016475:3T3 Cells / Q000187:drug effects / Q000528:radiation effects; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001483:Base Sequence; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D004249:DNA Damage; D051379:Mice; D008969:Molecular Sequence Data; D017239:Paclitaxel / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014747:Vinblastine / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D014747:Vinblastine; D017239:Paclitaxel