| Objective: The incidence of esophageal cancer is very high among all malignant tumors,as a traditional medicine for the treatment of cancer,fluorouracil plays critical roles in the treatment of malignant tumors of digestive tract.In order to further explore the application potentiality of antitumor drugs 5-fluorouracil(5-Fu)in the treatment of esophageal cancer,we tested the growth inhibition and ability to induce apoptosis of 5-fluorouracil and fluorouracil implants on esophageal TE-1 cell line by in vitro experiments,and exploring the effective concentration and function time to induce apoptosis of tumor cells,which could provide laboratory basis for clinical reasonable chemotherapy regimens.Furthermore,the safety and efficacy of fluorouracil implants in the treatment of esophageal cancer was further verified by clinical case studies.Methods: Part 1 we used human esophageal carcinoma cell line TE-1 as the cell model,which was cultured in vitro,and treated with 5-fluorouracil and fluorouracil implants respectively,cells were counted at different time points.In order to find out the drug concentration and action time for significant apoptosis,we used the apoptosis kit to detect the influence on the growth of TE-1 cells with different concentration and time treated by 5-fluorouracil and fluorouracil implants for the purpose of screening out the best drug concentration and processing time.The specific experimental design includes the following two aspects:(1)inhibition of cell proliferation on TE-1 by 5-fluorouracil: We set four concentration of 5-fluorouracil group,namely 0?g/ml,10?g/ml,50?g/ml,100?g/ml,and then treated the TE-1 cell with 24 h,48h,72 h and 96 h respectively,and finding out drug concentration and action time with significant apoptosis by cell counting,and then using the apoptosis kit to detect apoptosis.(2)inhibition of cell proliferation on TE-1 by fluorouracil implants: We used fluorouracil(HPLC grade)as the internal standard and drawing the standard curve for measuring the concentration of fluorouracil with different releasing time by high performance liquid chromatography(HPLC),and then treated the TE-1 cells with 24 h,48h,72 h and 96 h,in order to find out the best drug concentration and action time with significant apoptosis.Part 2 under endoscopy,we dividing the whole focus into several layers by each 1.0cm and implanting one slow-release particles(about 10 mg)in each point whose interval is 1.0 cm.One course of treatment includes three-time implantation and each treatment needs four weeks,by the way the details depend on the state of illness.In this research,all of patients complete the treatment smoothly.By comparing the patients' situation of before treatment,three-month treatment and six-month treatment,which include the remission of clinical symptom,the changing of focus area,the improvement of swallow function,untoward effect and life quality,et al.Results:(1)the inhibition of cell proliferation on TE-1 by 5-fluorouracil was highly correlated with the drug processing time,and the concentration of 10?g/ml had an obvious effect of TE-1,but increasing the drug concentration did not significantly increase the effect of drugs,moreover,there was obvious difference when treated with 96 h,but we could not detect obvious apoptotic body.(2)we found that the slow-release particles release increased gradually with the extension of time by using high performance liquid chromatography(HPLC)for determination of the release amount of fluorouracil implants,and the concentration maintained a basic balance for 48 h,and the concentration of latter treating was a bit lower,fluorouracil implants in TE-1 cells had different effects with different time,furthermore,the cell number reduced obviously when treating for 48 h to 72 h,and the concentration was 282?g/ml,the more obvious effect was detected with longer treating,and we could detect apoptotic bodies clearly.(3)The results show several test indexes changed a lot.When treated for 3 months and 6 months,the levels of focus area and swallow difficulty classification were decreased significantly(P<0.05)as compared with those before treatment;but the life quality of patients did not have significant statistical difference(P>0.05),by the way there is no individual difference appearing because of a little short of testing time and a few of samples.In addition,The WBC had a significant statistical difference between before treatment and three-month treatment(P<0.05),and the ratio of complication didn't have a significant change.Conclusion: 1 Fluorouracil injection and fluorouracil implants could inhibit the proliferation of human esophageal cancer cell lines.2 The concentration of fluorouracil implants was stable,which could promote the apoptosis of esophageal cancer cell line TE-1,and the effect was highly correlated with the drug treatment time.3 The therapeutic effect of fluorouracil implants on esophageal cancer cell line was significantly better than that of Fluorouracil injection.4 Endoscopic implantation of 5-FU slow-release particles for the treatment of advanced esophageal carcinoma is a safety,high efficacy,low toxic and better tolerant palliative treatment. |
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