PARENT SESSION
1:30 PM to 3:30 PM
Tuesday, April 23, 2002
Poster Session 21 Radiation-Drug Interaction
Room: Nevada Exhibition Center
(P26-273) Enhanced apoptotic effects of taxoltere pnip combined with radiation.
Yang, Li-Xi*,1,2, Zhu, Jun1, Wang, Hui-Juan1, Holton, Robert3, 1 California Pacific Medical Center Research Institute, San Francisco, California2 St. Mary's Medical Center, San Francisco, California3 Department of Chemistry, Florida State University, Tallahassee, Florida
ABSTRACT-
Paclitaxel has shown antitumor activity in a number of tumors and chemoradiosensitizing effects on some tumor cells. A novel paclitaxel analog, taxoltere pnip, has been synthesized by Dr. Holton and tested in our laboratories. This new taxane compound has exhibited markedly higher anticancer activity on several tumor cell lines in vitro and substantial chemoradiosensitizing effects on mouse mammary adenocarcinoma in vivo. In this study, effects of taxoltere pnip with or without radiation on non-small cell lung cancer cells (H23 cells) were evaluated in vitro. Using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) method, apoptosis in H23 cells was determined after drug treatment +/- radiation. The results demonstrated that taxoltere pnip remarkably induced apoptotic H23 cells and mitotic arrest after drug exposure. Taxoltere pnip was significantly more effective against H23 cells than paclitaxel. Combination of taxoltere pnip with radiation yielded many more apoptotic H23 cells than drug or radiation alone. Chemoradiosensitizing effects of taxoltere pnip (SER = 2.04) were significantly higher than those of parent drug, paclitaxel (SER = 1.71). The data indicated that taxoltere pnip could efficiently chemoradiosensitize non-small cell lung cancer cells and apoptosis might be an important mode of cell death caused by treatment with taxoltere pnip +/- radiation. The studies on the molecular interaction of taxoltere pnip with radiation would greatly contribute to development of taxoltere pnip as a new chemoradiosensitizing agent. This research was supported in part by a grant (9RT-0172) from UC TRDRP.
KEYWORDS: Apoptosis, Taxane Analog, Anticancer drug, Chemoradiosensitization