Effect Of Letrozole On Migration And Invasion Of Breast Cancer MDA-MB-231/ERα Cells

Background and Objective: Breast cancer is one of the most commonmalignant tumors of female, seriously endangers the physical and mental health ofwomen. Due to lack of corresponding receptor, hormonal therapy and target therapyhas no effect on the triple negative breast cancer. It is the main cause of poorprognosis of triple negative breast cancer because it prone to metastasis to lung andliver. Due to lack of corresponding receptor, hormonal therapy and target therapy hasno effect on the triple negative breast cancer. It is the main cause of poor prognosis oftriple negative breast cancer because it prone to metastasis to lung and liver. It wasoccasionally reported that triple negative breast cancer turn to express ER in clinic,but there has not been reported about letrozole may improve the effect of treatment inthe breast cancer which transform from the ER receptor-negative to ER-positive. Thistopic is intended to further explore letrozole on migration and invasive ability ofhuman breast cancer MDA-MB-231/ERα cell line and its mechanism through a seriesof in vitro studies, and to provides a new theoretical basis for this kind of drugsapplication in the treatment of triple negative breast cancer.Methods:(1) MTS assay was performed to measure the effect of letrozole aloneand with cyclophosphamide on breast cancer cell growth and proliferation;(2)&(3)Scratching assay and transwell method were used to measure the effect of letrozole onthe migration and invasion/metastasis abilities of MDA-MB-231/ERα cells in vitrorespectively;(4) Real-time PCR was used to detect LRP16gene mRNA levels in eachgroup;(5) The changes of Aromatase, E-cadherin and MMP-2expression afterletrozole treatment in MDA-MB-231/ERα cells were surveyed by Western blotting.Results：(1) Inhibition of single use of letrozole on MDA-MB-231/ERα cell growth was very weak, and inhibition of MDA-MB-231/ERα by20μg/L letrozole at72hours was to19.2%;(2) Letrozole significantly inhibited migration ofMDA-MB-231/ERα cells, and cell confluency of treatment group decreased10.2times compared to control group;(3) Letrozole reduces invasion ability ofMDA-MB-231/ERα cell, and cells trans-membrane of letrozole treatment group(20.0μg/L) was significantly lower than that in control group (respectively,6.0±0.51and95.1±8.46), the difference was significant (P<0.01);(4) Letrozole can down-regulatethe expression of ER co-activity factor LRP16mRNA level in a dose-dependentmanner.(5) Letrozole can down-regulate the expressions of Aromatase and MMP-2,and up-regulate the expression of E-cadherin in a dose-dependent manner.Conclusion:(1) Letrozole cannot solely effectively inhibit proliferation of humanMDA-MB-231/ERα breast cancer cells in vitro;(2) Letrozole can inhibit the abilitiesof migration and migration/invasion in vitro of human breast cancerMDA-MB-231/ERα cell;(3) Letrozole may inhibit MDA-MB-231/ERα cell invasiveability of the movements and migration by inhibiting aromatase and thereby reduceexpression of LRP16, MMP-2and MMP-9and increasing the expression ofE-cadherin protein.