| It is widely known that china is an esophageal carcinoma high risk area.Human health are highly threatened.The therapy for eso phageal carcinoma,gives more priority to operative treatment,combi ning with chemotherapy,radiotherapy and biotherapy.Most patients are in the middle-late stage at their first visit to the hospital cause of in clinical symptom of esophageal carcinoma.So chemotherapy is performed as the important auxiliary medication before and after op eration of esophageal carcinoma.However,many disadvantages exist in the common-used chemotherapeutant,such as drug-resistant,serio us poisonous side effects,obvious untoward effect,and their relative expensive prices.Based on the above reasons,we should discover t he chemotherapeutant,which can overcome the drug-resistant in the cancer cells,have less side effects,relative cheap and strong antican cer abilities.Curcumin is a polyphenolic compound extracted from curcuma genus of zingiberaceae.Some researches show that,curcumin have a ntiinflammatory,antioxidation,anticancer properties and no toxic side effects.Curcumin can inhibit some drug-resistant cells,such as live r cancer and lung cancer cells from growing.As the researches mov e long,one of the main mechanisms is by inducing cell apoptosis.But it has not been reported that curcumin have the ability of anti-d rug-resistance of esophageal carcinoma in China.It's worth studying on whether or not curcumin suppresses drug-resistant esophageal carcinoma cells growth and it related with indu cing tumor cell apoptosis.In order to investigate the effect of curcumin on growth in xenograft of human esophageal carcinoma drug-resistant cells in nude mice and the relation with induces tumor cells apoptosis,human esophageal carcinoma drug-resistant cells Eca-109/VCR xenograft was established in nude mice and randomly divided into four treatment groups(n=6): control group,VCR group,curcumin group,and VCR combined with curcumin group(combination group).Dynamic detection of tumor volume and draw tumor growth curves.After the 20 st day of treatment,the nude mice were dissected and the tumors were taken off,and the tumor volume and weight were measured,and the tumor growth inhibition rate was calculated.The tumor was examined by histopathology with HE staining.The cell apoptosis was detection by TUNEL dyeing method.The protein levels of Caspase-8,Caspase-9 and Caspase-3 in the xenografts were examined by ELISA.We compared gene expression in tumor of the control group and the combination group using human apoptosis real-time PCR microarrays consisting of 84 genes.It was found that the tumor volume and mass of nude mice in the control group,VCR group,curcumin group,and combination group was(1.42±0.26)cm~3,(1.23±0.19)cm~3,(0.86±0.20)cm~3,(0.58±0.16)cm~3 and(1.34±0.24)g,(1.18±0.21)g,(0.82±0.16)g,(0.52±0.17)g,respectively.Compared with control group and VCR group,the volume and weight of xenograft in curcumin group and combination group were significantly smaller or lower,and the most significantly was combination group(P<0.05).Tumor inhibition rates of VCR group,curcumin group and combination group were 11.94%,38.56% and 61.44%,respectively.The HE staining showed that the xenografts of curcumin group and the combination group had a large number of necrosis,and the most extensive necrosis was observed in the combination group.The TUNEL dyeing method demonstrated that the apoptosis rate of xenografts in the control group,VCR group,curcumin group and the combination group was(15.25±2.53)%,(18.30±2.34)%,(42.72±1.74)% and(52.36±2.81)%,respectively,which is highest in the combination group.The ELISA results show that the protein levels of Caspase-8,Caspase-9,Caspase-3 in curcumin group [(7.79±1.48)?g/g,(5.79±1.09)?g/g,(9.05±1.50)?g/g,respectively] and combination group [(9.61±1.43)?g/g,(7.55±1.17)?g/g,(12.09±1.18)?g/g,respectively] were significantly higher than that of the control group[(4.50±0.83)?g/g,(3.03±0.33)?g/g,(4.57±0.94)?g/g,respectively] and VCR group [(5.23±0.68)?g/g,(3.35±0.60)?g/g,(5.69±0.80)?g/g,respectively](P < 0.05 for both).Human apoptosis real-time PCR arrays results shows among the apoptosis related genes,8 pro-apoptosis genes(CASP3,CASP8,CASP9,TNFRSF10 A,TNFRSF1A,TNFRSF9,TP73,TRADD)were significantly up-regulated,1 anti-apoptosis gene(BCL2A1)was significantly up-regulated.The result also shows that 1 inflammatory Caspase gene(CASP5)was significantly down-regulated.These results in this study demonstrated that curcumin can markedly inhibit the growth of human esophageal carcinoma drug-resistant cells Eca-109/VCR in nude mice and combined with VCR have a synergistic effect.The reason might be associated with induces tumor cells apoptosis and reverse multidrug resistance of the tumor.Curcumin may become a candidate for multidrug resistance of the tumor. |
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