ABSTRACT
【Objective】 To study the inhibitory effect of dihydroartemisinin （DHA） on triple negative breast cancer MDA-MB-231 cells and its mechanisms. 【Methods】 CCK-8 method was used to detect the inhibitory effects of DHA， artemisinin derivative， on the proliferation of triple negative breast cancer MDA-MB-231 cells. qRT-PCR and Western blot were used to test the expressions of CIZ1， Snail and TGF-β1 at mRNA and protein levels. After the exogenous application of TGF-β1 cytokines or TGF-β1 pathway inhibitor SD-208， Wound healing， Transwell invasion assay and Western blotting were performed to detect the effects of activation/inhibition of TGFβ1-smads pathway on the anti-metastatic effects of DHA and its mechanisms. 【Results】 DHA could significantly inhibit the proliferation of human breast cancer MDA-MB-231 cell lines in a dose-dependent manner. It could significantly suppress CIZ1， Snail， and TGF-β1 expressions at mRNA and protein levels in MDA-MB-231 cells. TGF-β1 cytokines treatment could enhance the migration and invasion ability of breast cancer cell， where TGF-β1 treatment also enhanced CIZ1， snail protein expression and smad2/3 protein phosphorylation level. DHA could reverse the above TGFβ1-induced effects. Furthermore， after the application of the TGF-β1 pathway inhibitor SD-208， the anticancer activity of DHA was enhanced， and the expressions of CIZ1， snail and phos-smad2/3 proteins were significantly inhibited. 【Conclusion】 DHA could significantly inhibit the proliferation and metastasis of breast cancer cells through suppressing the TGF-β1/Smad and CIZ1 signaling.
ABSTRACT
Purpose To discuss the clinical,histopathological characteristics,diagnosis,differential diagnosis and prognosis of malignant intraductal papillary lesions of the breast.Methods 28 cases of malignant intraductal papillary lesions of the breast were analyzed by histology and immunobistochemistry.Clinical and follow-up information was obtained.The published relevant literatures were reviewed.Results All the patients were females with a mean age of 55.7 years.The clinical features were a palpable mass or nipple discharge.28 cases were diagnosed including 22 cases of intraductal papaillary carcinoma,2 cases of encapsulated papillary carcinoma and 4 cases of solid papillary carcinoma.Microscopically,the tumor showed solid and papillary area inside the capsule wall with fine delicate fibrovascular septa.The tumor cells usually displayed low-grade nuclear features.Immunohistochemistry,the tumor cells revealed diffusely strong positive ER and PR in almost all cases and HER-2,CK5/6 were negative positive.All cases were negatiive for CK5/6,p63 and SMA in the celluar nodules.CD56,Syn and CgA were found positively in some solid papillary carcinoma cases.The average positive rate of Ki-67 in tumor cells was 5.3 ％.27 patients were available for follow-up examination from 10 to 79 months and all the patients were alive.Conclusion Malignant intraductal papillary lesions of the breast most occurs in postmenopausal women.The diagnosis should be based on the clinical information,histopathological features and immunohistoehemistry stain due to its diverse histology.The main differential diagnosis is intraductal papilloma.This kind of lesion is a low grade malignant tumor with favorable prognosis.