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The Radiosensitizing Effect Of Taxotere On Human Nasopharyngeal Carcinoma Cell Line CNE-I

Posted on:2003-09-18Degree:MasterType:Thesis
Country:ChinaCandidate:Q TangFull Text:PDF
GTID:2144360092996120Subject:Oncology
Abstract/Summary:PDF Full Text Request
PrefacePeople find that some anti-neoplastic drugs probably still have a radiosensitizing effect except that possess the cytotoxicity effect. Because anti-neoplastic drugs have advantage that other drugs have not as radiosensitizer in clinical practise. Paclitaxel and docetaxel represent a novel class of anti-neoplastic drugs that bind specifically to mi-crotubles. There has been much investigation of, and debate over, the ability of Taxol to sensitize cells to radiation, While Taxotere has not been investigated to the same extent. Taxol has been reported to sensitize a variety of cell lines to radiation. These include G18,HL60 and OVG-1. Rodriguez and Rave-Frank-M et al. reported that Taxol had modest radiation-sensitizing effects in cervical cancer cell lines (ME18(KSiHa,MS75UMCF-7andCASki). Liebmann et al. also reported that the A549 cell line was not sensitized by Taxol. Using a treatment protocol of radiation followed by Taxol, it has been shown for HeLa cells that if there is an interval between the radiation treatment and the initiation of Taxol exposure, sub-additive, additive or supra-additive effects can be observed depending on the interval (Tal-war and Redpath ). Data on Taxotere is very limited although it is the drug of choice in many hospitals due to side-effect reduced and greateravailability compared with Taxol. It is a potent anti-cancer drug that is prepared from a non-cytotoxic precursor extracted from the needles of Taxus baccata, but its action on microtubules appears to be both quantitatively and qualitatively different from Taxol. The aim of this study was to investigate the ability of Taxotere to radiosensitize human naso-pharyngeal carcinoma cell line CNE-I by colony-forming assay.Materials and MethodsCells were grown in PRMI1640 medium with Hank's balanced salts ( GIBCO) and 10% fetal calf serum, and cultured in flaks in incubators with 37 ,5% C02. The exponetial growth phase cells were trypsinized and counted. For cytotoxicity experiment , the cells were plated in 60mm dishes with 5ml of medium and allowed to attach for a-bout 12 h. The number of cells is 400. Following an incubation period (3h) with different drug concentration (or PRMI1640 alone) , medium was removed by aspiration, and 8 ml of medium free drug were added back. Dishes were then incubated for 14 days. Cells were fixed in 95% methanol and stained with crystal violet, and colonies more than 50 cells were counted . For radiosensitizing experiment, the experiment was divided negative group ,simple drug group ,simple radiation group and radiation plus drug group. Drug alone or radiation plus drug group were added medium containing different concentration Taxotere(l 10-6,2 10-7,1 10-8mg/ml) ; Control group was only added medium free drug. The number of cells per dish was chosen such that 100 -200 colonies would survive after a specified treatment. The cells were continued to incubate 3,6,24 h, the medium was removed by aspiration, and cells were washed twice with sterile phos-phate-buffered saline, then 8 ml of medium free drug was added back. RT and RT plus drug group were radiated 1 ,3,5 7,9Gy. Then the dishes were incubated in free drug medium for 14d. Three plates were prepared for each concentration and dose of irradiation in experiment, and the experiment was done twice. Cells were fixed and stained, and colonies were counted. Cell growth curves were drawn using SPSS and Origin statistics software , Sensitizer enhancement ratios ( SERs) at 10% survival were evaluated.Results1. Cytotoxicity of TaxotereThe significant cytotoxicity of Taxotere was demonstrated at these concentrations. Cytotoxicity was dependent on drug concentration. The 35% ,50% ,70% ,and 90% inhibition dose (ID35,ID50,ID70, ID90) of Taxotere were 1 10-8mg/ml , 3. 2 10-8 mg/ml, 2 10 -7mg/ml and 1 10 -6mg/ml,respectively.2. Effects on CNE-I cells of pre-treatment with Taxotere followed by irradiationThe cell surviving curves demonstrate the radiosensitizing potential of Taxotere. The Taxotere plus radiatio...
Keywords/Search Tags:Taxotere, Nasopharygeal carcinoma, Radiosensitizing
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