The Inhibitory Effects Of Ginsenoside Rg3Combined With Chemotherapyon Human Esophageal Squamous Cell Carcinoma Xenograft In Mice

Objective: Esophageal carcinoma is one of the most common malignantgastrointestinal tumors，it ranked sixth in the global cause of death due totumor. At present, the incidence of esophageal cancer is growing rapidly inAsia, particularly in China.The incidence of the disease at present can be up to100/105.At present patients with esophageal cancer mainly include operation,chemotherapy and radiotherapy techniques.With the development oftraditional medicine in recent years, research and development of anti-tumortraditional Chinese medicine is becoming a hot spot of concern.Ginseng is oneof the valuable Chinese herbal medicine,it has been isolated from ginseng inmore than40kinds of ginseng saponins monomer composition, includingginseng saponins Rg3belongs to the ginseng saponins glycol type.In recentyears, there are much attention has been paid to its anti-tumor effect graduallystudy.Researchs shows that the tumor growth and metastasis has obviousinhibiting effect. Ginsenoside Rg3is developed in our country at the sametime is a major component of the first application developed by our country inclinical anti-tumor traditional Chinese medicine “CanYi capsule”.It not onlyhas unique advantages in non-small cell lung cancer, but also is suitable forstomach cancer, colorectal cancer and other solid tumors.Past studies showthat ginseng saponins Rg3has inhibit the growth of cancer cells in vitro and invivo. However, ginsenoside Rg3anticancer mechanism is not clear.Relatedresearch reports, ginseng saponins Rg3can significantly reduce the cancer cellproliferation, angiogenesis and metastasis. So the ginseng saponins Rg3islikely to be effective cooperated with chemotherapy drugs, in order to improvethe chemotherapy of tumor suppression function. This research will use theanimal model to observe the changes of tumor volume and weight in Eca-109 esophageal cancer xenograft in nude body, through the blank control group,single medicine ginseng saponins Rg3group, chemotherapy group(TAX+DDP), combined chemotherapy group (ginseng saponins Rg3plusTAX+DDP). the difference between the comprehensive analysis of ginsengsaponins Rg3in combination with chemotherapy for esophageal cancer innude mice transplantation tumor model of transplanted tumor growth.Andfurther the expression of Ki-67in occlusion of the dome and MVD(microvessel density) of the microvascular density shoud be analysed, in orderto investigate the ginseng saponins of Rg3in combination with chemotherapyin the treatment of esophageal cancer transplanted tumor effect.Further theseguide clinical selection of chemotherapy drugs and compatibility, and providenew train of thought and theory basis.Methods:1The models of the esophageal squamous cell carcinoma(Eca-109)xenograft transplanted in in the right forelimb of BALB/c nude micewere established.The tumor-bearing mice were randomly assigned to fourtreatment groups: blank control group, single drug Rg3(Rg3), chemotherapygroup (TAX+DDP), combined chemotherapy group (Rg3+TAX+DDP),The mice were randomly assigned to4groups (n=5). Group of single-agentRg3(6mg/kg/d, every day to fill the stomach, for3weeks), chemotherapygroup (taxol,10mg/kg/d, cisplatin,5mg/kg/d, abdominal cavity medicineinjection, respectively in,7,14,211day), combined with chemotherapy group(Rg3combination), blank control group with0.9%sodium chloride injectionvolume.2Tumor size was measured every other day, and the tumor volumes (cm3)were estimated according to the following formula:(0.52×length×width2).21days after the death in mice weighing tumor weight, calculate tumor inhibitionrate.3Esophageal squamous carcinoma using immunohistochemical detectingtechnology to explore nude mice transplantation tumor of Ki-67expressionand microvascular density (MVD) expression changes, difference between comparison and analysis.4Statistical analysis of the data by SPSS13.0software.Measurement datatox±SD said, many sets of sample mean comparison between using singlefactor variance analysis, P <0.05for the difference was statisticallysignificant.Results:1During the period of study medication, four groups of mice did notappear mice death cases.4groups are not Significant drug-related adverseevents.2Groups of nude mouse transplantation tumor growth volumemeasurement. Rg3group of treatment before the blank control group,single-agent,chemotherapy, combination chemotherapy group, the nudemouse transplantation tumors present product is respectively:(0.135±0.135)cm3,(0.126±0.020) cm3,(0.146±0.018)cm3and (0.141±0.016) cm3(P=0.249), there was no significant difference among the groups.Daily inobservation on time after drug treatment, drug use after3days, each tumorgrowth differed, single-agent Rg3tumor-burdened group, chemotherapy groupand chemotherapy group nude mice transplantation tumors had productcompared with blank control group decreased significantly (P <0.001).15days combined with chemotherapy group a tumor-burdened nude micetransplantation tumors appeared difference, significantly lower than the otherthree groups (P <0.0001). Medication blank control group, only21daysmedicine Rg3tumor-burdened group, chemotherapy group and chemotherapygroup nude mice transplantation tumors had product is respectively:(2.578+2.578) cm3,(1.918+0.1060) cm3,(1.157+0.122) cm3and (0.610+0.089)cm3(P <0.0001), according to the volume of tumor growth and tumor growthcurve drawing time relationship.3Groups xenograft tumor weight and tumor inhibition rate Rg3group,21day single-agent chemotherapy group, the combined group transplantedtumor weight was significantly lower than the control group (P <0.05), Rg3group in the single-agent chemotherapy, combination chemotherapy inhibited tumor growth rate were24.37%,59.67%and70.64%.4Groups of nude mice using HE staining and Ki-67the MVDimmunohistochemistry of resultsLight microscope, blank control group, HE staining visible rich tumorcells, cell sizes, Rg3group of single-agent chemotherapy, combinationchemotherapy group were visible tumor tissue, but the combined group (TAX+DDP+Rg3) tumor cell nucleus quality low color depth than the rest of thegroup, the nucleus small, more visible shrinkage in the tumor tissue, densecytoplasm, the enhanced eosinophilic staining cells.Ki-67light microscope combined with chemotherapy group (TAX+DDP+Rg3) was significantly lower than in the other groups. Groups MVDmicrovessel density visible chemotherapy group (TAX+DDP+Rg3) wassignificantly lower than the rest of the group.Conclusion：Ginsenoside Rg3combined with paclitaxel plus cisplatinchemotherapy with blank control, single-agent Rg3(Rg3), chemotherapygroup (TAX+DDP) compared to significantly inhibit tumor cell growth andproliferation. Detection of Ki-67and MVD, the results suggest thatginsenoside Rg3combined with paclitaxel plus cisplatin chemotherapy werelower compared with the other three groups of indicators, to consider furtheranti-angiogenic effect of ginsenoside Rg3increase the efficacy ofchemotherapy.