Predictive Value Of FHL1 In Breast Cancer Neoadjuvant Docetaxel And Anthracycline Chemotherapy

Neoadjuvant chemotherapy(NCT)has been an important component of multimodality treatment for Breast cancer.However,about 27%of the patients did not benefit from this clinical treatment and,predictive factors of response were not defined yet.This study was designed to evaluate the value of the four and a half LIM domains 1(FHL1)to predict response in stageⅡandⅢbreast cancer patients treated with taxane and anthracycline combination as neoadjuvant setting.FHL1 was regard as a cancer suppressor gene in most human tumor.This study was divided into three part.Firt part of all,164 patients received preoperative Pirarubicin(THP)(50 mg/m2)in i.v.infusion in D1 and combination with Docetaxel(75 mg/m2)in D2 every 3 weeks after core needle biopsy.Their clinical and pathological material were retrospectively analyzed,and slides of 67 patients have been got matched at last.Clinical and pathologic response rates were measured after preoperative therapy.Expression level of FHL1 was investigated in immunohistochemistry (IHC)stains.We evaluated the response rate to neoadjuvant chemotherapy and the predictive significance of immunohistochemical(FHL1)outcomes.As a result, FHL1 protein expression decreased after chemotherapy,overexpression was associated with lower clinical response rates.The second part,FLAG-tagged FHL1 and empty vector was transfected into breast cancer cells,MCF-7,and the stably transfected cell strains was constructed. MCF-7 cells transfected with FHL1 and empty vector both were diveded into four groups,and then respectively cultured in regular medium,and gave different chemotherapy agents seperately.At specified times,cell numbers were determined by crystal violet assay.Values shown are mean±SD of triplicate measurements and have been repeated 3 times with similar results.Results showed that,both Docetaxel and THP could suppress the growth of cells with or without FHL1-overexpression,and Docetaxel led lower decrease in the number of alive cells than THP.FHL1 had not significantly affect on the response to different chemotherapy agents of the cells.The third part,cells stably transfected with FHL1 were treated with four different agent regimen,include blank control.Proteins extracted from above cells lines were analyzed by Western blot with anti-FHL1.The densitometric quantitation of FHL1 bands normalized to GAPDH.The results showed that Docetaxel was the main contributor to decrease the expression of FHL1.In sum,as a tumor suppressor,expression of FHL1 in breast cancer was an important predictive factor in neoadjuvant chemotherapy.And higher level of FHL1 in breast tumor means lower clinical respons to chemotherapy.Docetaxel could decrease the expression of FHL1 in breast tumor,may promote anchorage-independent cell growth and migration.