A Study Of Effects Of Metformin In BALB/c Mouse Model Of Breast Cancer By Micro PET/CT

Purpose:1.To investigate the therapeutic effect of metformin in BALB/c mice with breast cancer through animal experiment.2.Micro PET/CT was used to evaluate the therapeutic effect of metformin in BALB/c mice loaded with breast cancer.3.The expression of ki-67 antigen protein in metformin-loaded BALB/c mice was investigated by histopathology and immunohistochemistry.Method:1.Establishment of BALB/c mouse model with breast cancer:Breast cancer 4T1 cells were purchased from Procell Biotechnology Co.,LTD.BALB/c mouse model of breast cancer was established by culturing and collecting cells.Twelve healthy female BALB/c mice of 4-6 weeks were selected,all weighing 15±3g,and each mouse was subcutaneously injected with 5×105 cells/200uL4T1 cells under the right axilla to observe the survival of BALB/c mice with breast cancer,the growth rate and size of subcutaneous tumor.2.Metformin treatment for breast cancer BALB/c mice:metformin hydrochloride powder(100mg)was dissolved with 12mL normal saline to prepare metformin hydrochloride solution with a concentration of 50mM.Twelve BALB/c mice were randomly divided into metformin group and control group,respectively,with metformin hydrochloride solution 400uL/mouse(200mg/kg)and the same volume of normal saline,once a day for 2 weeks.The growth rate,size and morphology of subcutaneous tumor nodules were observed and recorded.3.Micro PET/CT imaging:micro PET/CT imaging was performed both before administrationand 14 days after.Before imaging,BALB/c mice with breast cancer were fasted for 8h and injected with about 9.25×109Bq(250uCi)18F-FDG in the tail vein.Imaging was performed 1h later to compare whether there were differences in SUVmax and size of subcutaneous tumor nodular between groups4.Twelve BALB/c mice with breast cancer were sacrificed and the tumor tissues were removed and sent to the pathology department for HE staining and immunohistochemistry to compare the morphological changes of tumor cells and the positive rate of ki-67 antigen protein between groups.Results:1.The growth of subcutaneous tumor nodules in BALB/c mice with breast cancer was good,and there was no significant difference in weight(P>0.05).After drug intervention,the growth rate of subcutaneous tumor nodules in metformin group was slower than that in control group(tumor doubling time 3.54±0.82 days&2.12±0.51 days),the statisticalresults were significant(P=0.027),and the tumor doubling time in metformin group was longer than that in control group.At the end of treatment,the volume of subcutaneous tumor nodules in metformin group was significantly smaller than that in control group(352.46±55.01mm3&697.53±67.21mm3),and the statistical results were also significant(P<0.001).2.In PET/CT imaging of BALB/c mice with breast cancer,the diameter of subcutaneous tumor nodules in metformin group was smaller than that in control group(0.9±0.21cm&1.5±0.14cm,P=0.049),and SUVmax of subcutaneous tumor nodules in metformin group was smaller than that in control group(0.36±0.04cm&2.55±0.18,P=0.038),the statisticalresults were significant,which suggesting that the glucose metabolism level of subcutaneous tumor nodules in metformin group was significantly lower than that in control group.3.There was no significant difference in tumor morphology between the two groups of BALB/c mice.The positive rate of ki-67 antigen protein in metformin group was significantly lower than that in control group(26.7±5.1%&74.3±9.2%,P=0.013).Conclusion:1.Metformin can delay the growth rate of subcutaneous tumor nodules and prolong the tumor doubling time in BALB/c mice with breast cancer,which has a certain therapeutic effect on breast cancer.2.PET/CT can effectively evaluate the efficacy of metformin in the treatment of breast cancer3.Metformin can reduce the expression of ki-67 antigen in breast cancer cells.