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The Radiosensitization Of Paclitaxel On Nasopharygneal Carcinoma Cells (CNE-I) In Vitro And In Vivo

Posted on:2006-11-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:Z Y YuanFull Text:PDF
GTID:1104360185473583Subject:Oncology
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PURPOSE: To evaluate the effectiveness of the Paclitaxel combined with radiation on Nasopharygneal carcinoma cells (CNE-I) in vitro. METHODS AND MATERIALS: The human Nasopharygneal carcinoma cells CNE-I was used for this study. Cell survival was determined using clonogenic assays. DNA flow cytometry studies were performed to define the cell cycle characteristics of populations of cells that had been treated for 2-24 hours with 0, 0.5, 1.0, 2.5, or 10.0 nM paclitaxel. The cells were cultured with different concentration of paclitaxel for 24 hours before or after radiation. The radiation dose ranged from 0~10Gy. According to the G2/M block, the cells were cultured with paclitaxel of 2.5nM for 6 and 18 hours before or after radiation. Nude mice bearing transplanted human nasopharyngeal carcinoma on the right leg were used as Animal model, it received 2 different treatment schedules: (a) a single bolus of Paclitaxel 18 hours before radiation; (b) radiation followed by the same dose of paclitaxel. RESULTS: The IC10, IC50 and IC90 of the paclitaxel for CNE-I cells were 0.05nM, 1.0 nM and 2.5nM. The G2/M block was present when the drug concentration were 2.5 nM and 10.0 nM, and it peaked at the time of 18 hours. The presence of paclitaxel 0.05nM and 1 .OnM before or after radiation for 24 hours got the result of additive at the most radiation dose. Sixteen hours exposure in the 2.5nM drugs followed by radiation resulted in super-additive results, while the same exposure after radiation got the sub-additive results. When paclitaxel preceded radiation by 18 h, the combination resulted in synergism, with the TGD was 27 days and SER (sensitizing effect ratio) was 1.29. While for the schedule radiation followed by paclitaxel, the combination was sub-additive. CONCLUSION: On the basis of an optimal paclitaxel/radiation scheduling, paclitaxel exerted a radiosensitizing effect on CNE-I cells. The supra-additive effect is related to the G2/M block caused by paclitaxel.
Keywords/Search Tags:Radiosensitization
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