Bee Venom Acupuncture Point Injection Inhibits Groth And Metastasis As Well As Tumor Angiogenesis Of Lewis Lung Carcinoma In Mice And Its Mechanism

Background: Lung cancer is the most common malignant tumor,and is one of the important causes of cancer-related death,about 90% of lung cancer patients died of lung cancer metastasis but not lung cancer,while angiogenesis is a key step in tumor growth and metastasis.Unlimited growth,invasion and metastasis are dependent on angiogenesis,solid tumor growth period without vascular diameter of not more than 2mm,no tumor metastasis,when the tumor diameter reached 2mm,the need to continue to grow new blood vessels to provide enough oxygen and nutrients.No nutrients and oxygen vessels,tumors cannot continue to grow,and keep to the host state of harmlessness,angiogenesis in tumor growth from extravascular slow growth stage into the rapid proliferation stage with blood vessels,inhibiting angiogenesis can significantly control tumor growth and metastasis.Therefore,it is an effective method to inhibit tumor growth by inhibiting angiogenesis to inhibting oxygen and nutrition as well as diffusion channels.Melittin is bee venom gland and accessory gland secretes a strong pungent,bitter and sweet smelling a transparent liquid,stored in the poison sac,discharged from the sting sting sting.Many studies have shown that bee and moxibustion have inhibitory effect on tumor.Objective: This study put the application of bee venom(Bee venom)to intervente,taking Lewis lung cancer cells as target cells,combining with C57BL/6J mice;transplanted tumor volume and tumor weight as well as inhibition rate of lung cancer in mice are the measured and calculated;the number of tumor vessels were observed with microscope,the number of lung metastasis nodules in lung cancer mice were observed with microscope;detection of tyrosine(Janus kinase2,JAK2),tyrosine phosphorylation of 2(Phosphorylation-Janus,kinase2,p-JAK2)transcription factor 3(Signal transducer and activator of transcription,STAT3),phosphorylation of the transcription factor 3(Phosphorylation-Signal transducer and activator of transcription,p-STAT3),cytokine signaling inhibitor 3(Suppressor of cytokine signaling,SOCS3),hypoxia inducible factor-1 alpha(Hypoxia inducible factor-1,HIF1 alpha),vascular endothelial growth factor(Vascular endothelial,Gro The expression of VEGF factor(wth),and the mechanism of point injection of bee venom to inhibit angiogenesis and metastasis of lung cancer from the perspective of JAK2/STAT3 signaling pathway.Methods: Lewis lung cancer mouse models were constructed;measuring the maximum and minimum diameter of tumors every day,calculating the tumors' volume and drawing the growth curve;in the 24 th day,anaesthetizing the draw materials and weighing the tumor,under the dissecting microscope,counting the pulmonary metastatic nodules;detecting CD34 calculating the microvessel density by immunohistochemistry,using drug to effect on the angiogenesis in tumor section of Lewis lung carcinoma;observing the drug's effect on relative protein of JAK2/STAT3 signal passage by Western Blotting method;observing the expression of VEGF by immunohistochemistry,observing the expression of HIF-1? and VEGF mRNA by qPCR method.Results: Tumor growth was significantly inhibited after BV acupuncture compared with non-point injection of BV(P<0.05),but no obvious difference was observed between non-point injection of BV and Avastin administration(p>0.05).However,BV acupuncture drastically inhibits lung metastasis,and prolonged the survival of LLC tumor bearing mice,as compared with subcutaneously injection of BV and Avastin(P<0.05).Intra-tumor MVD was significantly decreased in BV acupuncture group,as compared with other groups(P<0.05).Compared with mice treated with saline,an obvious reduction of pJAK2,pSTAT3,HIF-1? and VEGF had been observed after mice were treated with Avastin,non-point injection of BV,and BV acupuncture.The level of SOCS3 was dramatically upregulated in BV and Avastin groups(P<0.05).By real time fluorescence quantitative PCR detection,HIF-1?,VEGF mRNA,Avastin group,non acupoint group and bee venom acupoint injection group were significantly lower than those in the control group(P<0.05),bee venom group was significantly lower than that in the bevacizumab group(P<0.05),bee venom group was significantly lower than that in the bevacizumab group(P<0.05).Point injection of bee venom venom group was significantly lower than that of non meridian group(P < 0.05),bee venom group and bevacizumab group had no significant difference(p>0.05),the expression of SOCS3 mRNA,bevacizumab group and point injection of bee venom melittin group was significantly higher than that of non acupoint group and normal saline group(P < 0.05),bee venom group higher than the bevacizumab group(P<0.05),bee venom group was significantly higher than that in the bevacizumab group(P<0.05).Conclusion: BV acupuncture point injection conferred a significant metastasis inhibitory effect and anti-angiogenesis through inhibiting JAK2/STAT3 signaling pathway compared with non-point injection of bee venom.