Effects Of VitaminD₃or Combination With5-Fluorouracil On Growth Of Human Esophageal Carcinoma109Cells Xenografts Tumor

Objective：To investigate effects and mechanism of1,25-（OH）₂Vitamin D₃aloneor combination with5-Fluorouracil on human esophageal carcinomaEca-109cell xenografts tumor.Methods：In vitro,cultured human esophageal carcinoma Eca-109cell line,Eca-109cell was injected subcutaneously on the right fore limbs of BALB/cnude mouse to establish the tumor-bearing model of human esophagealcarcinoma.The mouse were randomly devided into control group（C,n=5）,pretreatment group（PT,n=5）,vitamin D₃group（V,n=5）,5-fluorour-acil group（F,n=5）,pretreatment+5-fluorouracil group（PT+F,n=5）,vitaminD₃+5-fluorouracil group（V+F,n=5）.Two weeks prior to the beginning of theexperiment,group PT and group PT+F were received intraperitonealinjection of1,25-（OH）₂vitamin D₃solution （2.5μg/kg,once a day）; Four toeight days later,when the neoplasia formed, Group C and group PT were received intraperitoneal injection of saline （5ml/kg,once a day）,group Vwere received intraperitoneal injection with1,25-（OH）₂vitamin D₃solution（2.5μg/kg,once a day）,group F were received intraperitoneal injection with5-fluorouracil （25mg/kg,twice a week）,the dose and frequency in group PT+F and group V+F were identical with a single group,continuous processingfor two weeks. The growth of xenograft tumor was assessed by measuringtumor size with calipers every other day. Tumor volumes were calculated by（a×b2）/2.The expression of VDR mRNA and protein in tumor tissue of nudemouse were detected by Retrovirus polymerase chain reaction （PCR） andWestern blot. The serum calcium were tested by automatic biochemistryanalyzer,the calcium salt deposition were observed with von kossa dyeing inkidney.Results：The volume of tumor tissue in group C were statistically significantcompared with group PT、group V、group F、group PT+F、group V+F（P<0.05）;The expression of VDR mRNA and protein in tumor tissuecompared with group C were significantly upregulated in group PT、groupV、group F、group PT+F、group V+F （P<0.05）;The expression of VDRmRNA and protein compared with group PT、group V、group F weresignificantly increased in group PT+F、group V+F （P<0.05）; the expressionof VDR mRNA and protein in group F were significantly lower than group V（P<0.05）. The serum calcium level in PT group、V group、PT+F group、 V+F group was increased（P<0.05）, but there weren’t calcium deposition inthe kidney tissue sections.Conclusion：The growth of human esophageal carcinoma cell109xenografts tumorcan be inhibited by1,25-（OH）₂vitamin D₃、5-fluorouracil;In addition,thecombination of1,25-（OH）₂vitamin D₃and5-fluorouracil could exertsynergistic inhibitory effects on the growth of xenografts tumor.Themechanism of the inhibitory effects may be associated with the increasedexpression of VDR gene and protein.At the dose（2.5μg/kg） of1,25-（OH）₂-vitamin D₃,there were no calcium deposition occured in the kidney tissue ofthe tumor-beairng mice.