| Objective:Esophageal carcinoma is one of the most common malignant tumors inthe world and the sixth leading cause of death due to the tumor. Currently, theincidence of esophageal squamous cell carcinoma (ESCC) is growing rapidlyin Asian countries, particularly in China, with mortality rate approximating100/105. Radiotherapy and chemotherapy are the conservative treatments forESCC, but in recent years, with the development of science and technology,bio-targeted therapy becomes as a novel strategy. In1971, Folkman putforward the theory of tumor angiogenesis which if there is no blood vesselneogenesis, tumor diameter will be limited within2mm. The grwoth of ESCCwhich is a kind of solid tumor depends on blood vessel neogenesis. And bloodvessel neogenesis supplys nutrient for the tumor. The gene of blood vesselendothelium is stable, so drug resistance rarely occurs. So that gene becomesthe target of drug therapy, and it can be in long-term used with less resistanceand less side effects. Therefore, the anti-angiogenic therapy is very importantand requires further explore. Endostatin is a king of the antiangiogenesis.Endostar is the trade name of China-made rhES. Endostar combines withchemotherapy regimens treatment is efficacy in clinical trials for non-smallcell lung cancer. But the treatment efficacy evaluation of Endostar combinedwith chemotherapy was rarely reported. The purpose of this project is to studythe effects Endostar combined with chemotherapy which was gave to the nudemice with human esophageal squamous cell carcinoma (Eca-109). Then weobserved the inhibition of tumor proliferation and the apoptosis of cancer cells.The inhibitive effect of endostar combined with Paclitaxel+cisplatin on ESCCwas evaluated by comparison with group single chemotherapy, group single endostar, and group sodium, respectively.Methods:1Eca-109cells were lysed into single cell suspension in5×10~6cells (0.1ml) were subcutaneously injected into the left forelimb of BALB/c nude mice.2The mice were randomly assigned to4groups (n=5). Group1(controlgroup) was intraperitoneally injected0.9%saline only with0.2ml every dayfor3weeks. Group2(Endostar) was treated with Endostar at1.5mg/kg daywith the same volume by subcutaneous injection every day for3weeks. Ingroup3(chemotherapy), the combination regimen (Paclitaxel10mg/kg day,Cisplatin5mg/kg day) was administered intraperitoneally every1,7,14,21days. Group4(chemotherapy+Endostar) was received chemotherapy regimenin combination with Endostar using above the same treatments respectively.3The length (L) and width (W) of tumor were measured by using caliperevery other day and the tumor volumes (cm~3) were calculated. The weightswere monitored twice a week. After treatment the tumor xenografts wereexcised and weighed.4Immunohistochemistry Ki-67and Bax protein expression in the tumorxenografts of nude mice was detected.Result:1The mice were all observed tumor appearancing.2Before administration, the mean tumor volume of the control and testgroups was(0.128±0.027)、(0.120±0.056)、(0.110±0.026)、(0.115±0.011) cm~3（p=0.8552）. On the day3, tumor volume of mice inchemotherapy and chemotherapy+Endostar group started to appearsignificantly different from that in control and Endostar group (p <0.001). Onthe day15, the tumor volume in chemotherapy+Endostar group began toreduce and significantly lower than that in other three groups (p<0.0001) andkept that trence until the day21. On the day21, the tumor weight in control,Endostar, chemotherapy and chemotherapy+Endostar groups was as follows:(1.905±0.043),(1.380±0.053),(0.720±0.016) and (0.543±0.022) g. Theinhibitory rate of tumor in Endostar, chemotherapy and chemotherapy+ Endostar group was27.52,62.22and71.52%compared with control group.3Then tumor xenografts were used for histopathology assay by thehematoxylin–eosin (HE) staining. The tumors of chemotherapy+Endostargroup showed a low nuclearcytoplasmic ratio, small, and shadow-stainednuclei compared to other group. The chemotherapy+Endostar group causedtumor necrosis. Additionally, the expression of the proliferation marker Ki-67was significantly lower in tumor xenografts of the chemotherapy+Endostargroup compared with the other groups. The expression of the apoptosis factorBax was increased in tumor xenografts of the chemotherapy+Endostar groupcompared with the other groups.Conclusion:Endostar combined paclitaxel+cisplatin chemotherapy on nude micebearing human breast cancer Eca-109can inhibit tumor growth moresiginificantly than single chemotherapy. Our study provides the evidence onendostar combined chemotherapy in clinical treatment of ESCC. |
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