| Background and Objective:Currently,breast cancer is one of the most common malignant tumor which are threatening the lives and health of women in the world,Its development is fast and easy to transfer, and seriously affected the women's quality of life.According to statistics, every year in all female deaths due to cancer in women is about 13% of deaths because of breast cancer..Furthermore, the worldwide incidence of breast cancer showed a trend of increasing year by year, and the age of people with breast cancer also tend to be younger. Occurrence factors for breast cancer is very complex,such as the environment, genetic, lifestyle and so on?They all have a close correlation with breast cancer. Various fields such as clinical medicine have done much research on its mechanism ? treatment and so on. At present the choices of breast cancer treatment mainly are chemotherapy therapy ? endocrine therapy ?radiotherapy and surgery.But for Patients with advanced breast cancer who have lost the operation chance,endocre therapy has no effect on three negative breast cancer and as we all know, radiotherapy cannot selectively kill tumor cells, it will destroy the normal cells and tissue around the tumor at the same time, even cause bone marrow suppression. So that we commonly use chemotherapy drugs.However,the sensitivity of tumor chemothera Py drugs is low, and drug resistance and the damage to the body has been a huge obstacle in front of the clinicians and Patients,Based on the above factors, there is a desperate need for new safe and effective treatment method to improve survival and quality of life in Patients with advanced breast cancer.Low frequency ultrasound is a mechanical wave,Because of its characteristics of lower frequency, longer wavelength,,so it is easy to penetrate thetissue and absorbed less by tissue, as a result,it do less damage to normal tissue. The main biological effects of low-frequency ultrasound are cavitation, thermal effects and chemical effects, one of the most important is the cavitation effect.Lately,cavitation effect for tumor treatment is hot research topic.Cavitation is defined as follows.The tiny air bubbles existing in the liquid vibrate under the action of ultrasonic and when ultrasonic energy reaches a threshold value,the bubbles begin to occur a series of dynamic process of changes including rapid expansion, contraction,collapse and the enormous energy released at the same time.Vascellum is a necessary condition for tumor growth and metastasis, Studies of domestic and international have shown that cavitation can destroy the tumor blood vessels and increase the permeability of cell membranes to inhibit tumor growth. With the exploration and research of low-frequency ultrasound, it is increasingly being recognized that low frequency ultrasound can be as a novel means for cancer therapy,but it mainly are still in the experimental stage. Previous studies of the domestic and foreign research were limited to intervention therapy of low frequency ultrasound on tumor cells, such as prostate cancer cells, brain glioma cells, liver cancer cells, However there are less study of solid tumors. Breast cancer is the tumor depending on tumor blood vessels,the growth of blood vessels in breast cancer play an important role for growth and invasion of breast cancer. This research establish breast transplantation tumor model,then do different measures on breast tumor such as low-frequency ultrasound?chemotherapy drug. and after the interventions,through the evaluation of mice transplanted tumor volume change, tumor microvascular density and the expression of invasive blood vessel related protein(VEGF?MMP- 9?Notch1), so as to explore the curative effect of low-frequency ultrasound on transplanted tumor in mice and treatment mechanism of low-frequency ultrasound. Furthermore, to explore whether low-frequency ultrasound has this ability to enhance curative effect of Docetaxel on breast transplanted tumor.Methods:Firstly cultivate the breast cancer cells 4t1,and then inject the cells to breast padof the balb/c mice to build the 4t1-breast-bearing mice model.Sceondly calculate tumor volume and the inhibitory rate of groups(Tumor inhibition rate, TIR).TIR =(control tumor volume- experimental tumor volume)/control tumor volume by 100%.Thirdly Balb/c mice of breast cancer transplantation tumor model were randomly divided into four groups,treated by normal saline ? low frequency ultrasound ?docetaxel and combined treatment(low-frequency ultrasound + docetaxel). Then MMP-9?Notch1?VEGF protein expression of transplanted tumor were detected by Western blot,and used immunofluorescence to test CD34 which can mark tumor microvascular density(microvascular density. MVD).Results:Four groups of mice weight lifting.The tumor volumes of four groups were2192±741?1603±536?1211±879?975±506 respectively(P<0.05)The inhibitory rate of tumor were 0?28.5±22.4?45.6±27.1?55.6±23.1(P<0.05). Between four groups,the expression quantity of VEGF? MMP-9?Notch-1?CD34 were drop off in the following order:normal saline >docetaxel> low frequency ultrasound >combined treatment, the differences are statistically significant..The expression of CD34 and the expression of VEGF ? MMP-9 ? Notch1 was pearson correlation r=0.809?0.703?0.856(P<0.05).The expression of VEGF?MMP-9?Notch1 were pearson correlation,r=0.803?0.801(P<0.05),The expression of MMP-9 and Notch1 was pearson correlation r==0.715(P<0.05).Conclusion:The first Low-frequency ultrasound can inhibit the growth of tumor,significantly reduce the expression of VEGF?MMP- 9?Notch1 protein, inhibit the formation of tumor microvascular so as to control tumor growth, inhibite the angiogenesis?metastasis and invasiveness.The second Docetaxel can inhibit the growth of tumor, and reduce the expression of VEGF, MMP-9, Notch1 protein,inhibit the formation of tumor angiogenesis, but the effect is limited.The third Effect of combined treatment group compared with using low-frequency ultrasound and Docetaxel respectivelyin the inhibition of tumor growth and angiogenesis and in reducing of the expression of VEGF, MMP-9, Notch1 proteinare enhanced.The fourth, The expression of MVD marked by CD34 ? VEGF ? MMP-9 ?Notch1 are positively related, suppose low-frequency ultrasonic can make effect on tumor tissues according to the synergistic action of Notch signaling pathways ?VEGF pathwayand MMP-9 to inhibite tumor growth and metastasis. |
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