| Objective:To examine the expression of Dyrk1 B in the specimens of endometrial carcinoma and the endometrial cancer cells. To investigate the effect of Dyrk1 B inhibitor(AZ191) on cellular proliferation,apoptosis rate and the protein expression of Dyrk1 B.To discuss the role of Dyrk1 B in human endometrial carcinoma.Method: Human endometrial cancer cell lines Ishikawa(derived from well differentiated endometrial cancer), AN3CA(derived from undifferentiated endometrial cancer), HEC-1A and HEC-1B(both derived from moderately differentiated endometrial cancer) were incubated in vitro. The cell proliferation was detected by methyl thiazolyl tetrazo- lium(MTT) method after 48 hours of AZ191 with different concentration(0μM, 0.5μM, 1μM, 2.5μM, 5μM, 10μM, 25μM, 50μM, 100μM). The apoptosis rate after 48 hours of AZ191 with different concentration(0μM, 5μM, 10μM)was analyzed by flow cytome- try, and the protein levels of Dyrk1 B were detected by western blot. Immunohistochemistry staining method was performed in 174 patients with endometrial carcinoma, in 35 patients with endometrial precancerous lesions and54 patients with normal endometrial tissues to detect the expression of Dyrk1 B. The differences of Dyrk1 B expression between malignant endometrial tumors and normal endometrial tissues was compared and also analyzed the correlation of Dyrk1 B with clinicopathological parameters of endometrial carcinoma.Result: Compared with the control group, the cellullar proliferation was effectivelyinhibited after 48 hours of AZ191 with different concentration(0.5μM, 1μM, 2.5μM, 5μM, 10μM, 25μM, 50μM, 100μM)(P<0. 05). The apoptotic rate was significantly increased after 48 hours of AZ191 with different concentration(0μM, 5μM, 10μM). The protein levels of Dyrk1 B were decreased after 48 hours of AZ191 with different concentration(0μM, 5μM, 10μM). The level of Dyrk1 B was much higher in endometrial endometrial carcinoma group than that in control group(P<0. 05) [ 73.6%(128/174) VS 53.7%(29/54) ]. The levels of Dyrk1 B in endometrial carcinoma were not significantly diffe- rent with those in endometrial precancerous lesions [73.6%(128/174) VS 80%(28/35)]. The expression of Dyrk1 B had no correlation with the pathologic classification, grade and stage(all P > 0. 05), but associated with muscular infiltration depth and the level of serum CA125 and CA19-9(P < 0.05), respectively.Conclusion: Dyrk1 B is highly expressed in both endometrial carcinoma tissue and cell lines, AZ191 may promote cell apoptosis of endometrial cancer cell lines. Further,Dyrk1 B may be involved in regulating the proliferation and apoptosis of endometrial cancer cells, it may become a target in the adjuvant therapy of endometrial carcinoma. |
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