Expressions Of Notch1,c-myc And P21 In Breast Cancer And Effects Of Oridonin On Human Breast Cancer Bcap-37 Cell

The first partObjective: To investigate the expressions of notch1,c-myc and p21 in human breast cancer and the relationship with clinical pathology.Methods: The expressions of notch1,c-myc and p21 were examined in 60 invasive breast duct carcinoma cancer and 18 benign breast disease specimens using immunohistochemical technique.Results: The positive rate of the notch1,c-myc and p21 protein expression in breast cancer was 45.00%(27/60),60.00%(36/60) and 58.33%(35/60), higher than the rate in benign breast disease specimens 11.11%(2/18),22.22%(4/18),27.78%(5/18) (P<0.01). notch1 had closely relative to pathological differentiation (P<0.05) and lymph nod metastasis(P<0.01) of breast cancer, but not age and size (P>0.05); c-myc had no relative to pathological differentiation,age,size and lymph-node metastases of breast cancer (P>0.05); the expression of the p21 protein had negative correlation with lymph nod metastasis (P<0.01)but not with pathological differentiation,age and size. There was significant correlation between the expression of the notch1 protein and c-myc protein.(P<0.05).Conclusion: The positive rate of the notch1,c-myc and p21 protein expression in breast cancer was higher than the rate in benign breast disease specimens. notch1,c-myc and p21 protein maybe plays an important role in growth and invasion in breast cancer. notch1 had closely relative to pathological differentiation and lymph nod metastasis of breast cancer,it indicated that the expression of notch1 had relative to malignant of breast cancer and could help to judge prognosis of breast cancer. The second partObjective:To study the effect and molecular mechanism of oridonin on human breast cancer Bcap-37 cells lines.Methods:The growth inhibition rates of Bcap-37 cell were measured by MTT assay. Phase contrast microscope were used to observe the morphological changes of cells. Morphological changes in nucleus were defected by light microscope; The cell cycle were determined by flow cytometry; The mRNA expressions of notch1,c-myc,p21,cdc2 and cyclinB1 were assayed by RT-PCR.Results:Oridonin significantly inhibited the proliferation of human breast cancer cell line(Bcap-37) in a dose-dependent and time-dependent manner;After dealed with oridonin, the morphology of Bcap-37 cells changed ; The morphological changes of apoptosis, such as nuclear fragmentation or condensed particles were identified after incubation with oridonin by Hoechst 33258 fluorescent dyeing. Cell cycle analysis revealed that Bcap-37 cells treated by oridonin were blocked in G2/M phase; RT-PCR indicated that the mRNA expressions of p21 was increased, while the levels of cyclinB1,cdc2,notch1 and c-myc mRNA expressions were decreased in oridonin -treated Bcap-37 cells.Conclusion: Oridonin can inhibit proliferation of breast cancer Bcap-37 cells and induce Bcap-37 cells G2/M arrest, apoptosis and necrosis. The mechanism of cell cycle arrest may be associated with inhibition of notch1 signaling pathway.