| Objective:Breast cancer is one of women's the most common malignant tumor, accountingfor 13% tumor incidence in women, and the growth rate of global incidence is 0.2% -8% Tamoxifen (TAM) is the basic endocrine therapy of breast cancer drugs, may actdirectly on target organs, and compete for estrogen receptor, block its effect ,so it cansignificantly curb the incidence of breast cancer, markedly improved Postoperativesurvival rate , It has obvious effects in prevention of relapse, inhibiting the occurrenceof contralateral breast cancer, alleviating the disease and prolonging life. At thesame time It also has a weak estrogen-like effects, long-term applications caninterfere with the normal function of target organs, causing menstrual disorders,endometrial thickening, gland hyperplasia or atypical hyperplasia and polypoidchange, and even increase the incidence of endometrial cancer risk. Large doses ofprogesterone in breast cancer endocrine therapy is as second-line drugs, It has beenconfirmed by clinical practice,Currently,medroxyprogesterone acetate acetate andmegestrol acetate is considered to be more effective, progesterone hormone therapycan also be an overall improvement in the patient's clinical symptoms and improvesurvival quality, relieve pain and protect the bone marrow. Small doses ofprogesterone on the endometrium has a protective effect, can be used to prevent thecomplications of gynecological aspects. Based on high-dose progesterone for thetreatment of breast cancer cells, low-dose progesterone for endometrial protectionrole,in this experiment Small doses of medroxyprogesterone acetate is given toantagonist the weak estrogen-like effect on the target organ of tamoxifen, to restorate the normal function of target organs,to prevention and cure the tamoxifen-inducedcomplications of gynecological aspects.In this study, Estrogen receptor(ER)-positive MCF-7 human breast cancer is theresearch object ,to explore the low-dose megestrol acetate (MA) on the role of breastcancer cells, Will the combination of small doses of megestrol acetate and tamoxifenaffect the effectiveness of endocrine therapy, If it does, to explore the effects ofsynergy, antagonism, or no significant effect. It can Provide a theoretical basis inclinical application of small doses of progesterone drugs which is used to improve thecomplications of gynecological aspects caused by long-term TAM treatment.MethodsMethods:Culture the breast cancer cell line MCF-7; Estrogen receptor(ER)-positive MCF-7 human breast cancer cell line was treated by TAM or MA along,or in combinationin vitro. Growth inhibition was evaluated by MTT assay after 24 hours and 48 hours.Calculated the inhibition rate, Analysis the effects of interaction between the twodrugs according to the Jin's formula;Distribution of cell cycle and rate of apoptosiswere determined by flow cytometry(FCM) after 48 hours.Results:1,TAM can inhibit the growth of MCF-7 cells, After 24h and 48h, the inhibitionrates were 24.06% and 33.51%, compared with the control group the differences weremean, P <0.05; there was a slight growth inhibition in small dose of MA after24h and48h ,the inhibition rates were 10.38% and 23.91%, there was no significant differencecompared with the control group after48h, P> 0.05; there was Obviously enhancebetween the Combination therapy group and the single-drug group, , the inhibitoryrate are 44.48% and 53.79% after 24h and 48h, there was significant differencecompared with the control group ,P <0.05;2, TAM and MA could affect the MCF-7's cell cycle progression, the content of G1/G0 phase cells was significantly increased compared with control group, P <0.05;when small doses of MA combined with TAM, G1/G0 phase cells were increased,but there was no significant difference compared with TAM used alone, P> 0.05.TAM can induce cell apoptosis, there were statistically significant compared with thecontrol group P＜0.05; MA group had no significant apoptosis, there was nostatistically significant compared with the control group, P＞0.05. when two drugsare combined the difference was statistically significant compared with TAM usedalone, P <0.05.ConclusionConclusion:TAM can inhibit growth and induce apoptosis on MCF-7 cells, add the use ofsmall doses of MA, its growth inhibition and apoptosis rate is increased, There isSynergy in Combination therapy group.This experiment is in vitro, the result in vivois unclear now.Therefore, small doses of MA can be given to prevent and improve thecomplications which is cansed by long-term clinical use of TAM.
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