Objective To explore effect of DLL4 gene in MCF-7 cells of human breast cancer which was inhibitted by short hair in RNA （shRNA） on inducing apoptosis and chemosensitivity to docetaxel. Methods Specific shRNA was designed in accordance with DLL4 gene and transfected into MCF-7 cells of human breast cancer with liposomal （Lip-shRNA group）， MCF-7 cells transfected with only liposomal as Lip group， and control group without any treatment. Expressions of DLL4 protein in 3 groups were detected by immunohistochemical method， apoptosis and cell cycle distribution were examined by flow cytometry （FCM）. Proliferations and sensitivity of MCF-7 cells to docetaxel in 3 groups were determined by methylthiazoyl-tetrazolium bromide （MTT）. Results The averages optical density value and rate of positive area of Lip-shRNA group were significantly lower than that of other 2 groups （P＜0.01）. The levels of A value at 24h， 48h， and 72h in Lip-shRNA group were significantly lower than that of other 2 groups （P＜0.01）. Rates of cell apoptosis at 24h， 48h， 72h and 96 h in Lip-shRNA group were significantly higher than that of other 2 goups （P＜0.05），and ratio of G2/M was higher too （P＜0.05）. IC50 of Lip-shRNA group to docetaxel was significantly lower than that of other 2 groups （P＜0.05）. Conclusions The RNA interference technology can effectively block the expression of DLL4 gene. Inhibition of DLL4/Notch signaling pathway can lead to proliferation inhibition of cancer cell and a concomitant increase in cells undergoing apoptosis， and can enhance the cell sensitivity to docetaxel. DLL4 may be an important target for therapeutic approach of breast cancer.
Objective To study the expressions of Delta-like ligand 4 （DLL4） and S100A4 in breast carcinoma of differect molecular subtypes and explore its clinical significance. Methods The expressions of DLL4 and S100A4 in all molecular subtypes were tested by SP immunohistochemistry in 108 cases of breast carcinoma and 40 cases of paracancerous tissues from Taihe Hospital. The Luminal A， Lumianl B， HER-2 over-expression， and basal-like subtypes was 51， 26， 17， and 14 cases， respectively. Then the correlation of DLL4 and S100A4 expression with patients’ clinical and pathological features were analyzed. Results The positive expression rates of DLL4 and S100A4 in breast carcinoma was 67.6%（73/108）and 62.0%（67/108）respectively， which were significantly higher than those in paracancerous tissues〔22.5%（9/40） and 45.0%（18/40）〕， P＜0.05. The positive expression rates of DLL4 and S100A4 in breast carcinoma tissues of HER-2 over-expression and basal-like subtypes were significantly higher than those in breast carcinoma tissues of Luminal A and Luminal B subtypes （P＜0.05）. The expressions of DLL4 and S100A4 in breast carcinoma tissues with lymph node metastasis and without lymph node metastasis were significantly different（P＜0.05）. There was positiver elationship between the expressions of DLL4 and S100A4 in breast carcinoma tissues（rs=0.217，P＜0.01）. Conclusions DLL4 and S100A4 are highly expressed in breast carcinoma tissues of HER-2 over-expression and basal-like subtypes， and are all related with prognosis of breast carcinoma. These results suggest that they might be important factors in breast carcinogenesis and tumor development， metastasis. These proteins are indicators of metastasis and predictors for prognosis of breast carcinoma.