Expression And Clinical Significance Of Dyrk1b In The Specimens Of Cervical Lesions And Cells

Objective:To detect and explore the expression and clinical significance of Dyrk1 b in the speciemens of cervical lesions and cells. Methods:(1)All the date were collected from 75 patients with cervical cancer who visit to the First Affiliated Hospital of Dalian Medical University during January 2011 to December 2013 and confirmed by three-step screening and pathological examination, according to the International Federation of Gynecology and Obstetrics stages(FIGO), 60 cases were stage I, 15 cases were stage II; 12 cases were LSIL; 40 cases were HSIL; 28 cases with cervicitis were chosen as the control. The expression of Dyrk1 b were detected by immunohistochemical among four groups.(2)The expression of Dyrk1 b in Hela(HPV18 positive adenocarcinoma cell), Siha(pRb, p53 positive) and Caski(HPV16 positive) cells were detected by western blot and the expression of Dyrk1 b protein were detected after using AZ191(5μM, 10μM) for 48 h in Siha and Hela cells.(3)The cellular survival and proliferation of the cervical cancer cells were detected by MTT assay which include Hela, Siha, Caski, treated by different concentrations of Dyrk1 b inhibitor AZ191(0μM-100μM) for 48 h.(4)The rate of apoptosis of Siha and Hela cells was detected after 48 h treatment of AZ191(5μM, 10μM). Results:1. the positive rates of Dyrk1 b protein in chronic cervicitis, LSIL, HSIL and cervical squamous cancer by immunohistochemistry were 10.7%(3/28), 8.3%(1/12), 42.5%(17/40), 70.7%(53/75), The expression of Dyrk1 b in cervical squamous cancer and HISL were higher than that in LSIL and chronic cervicitis(P<0.01), the difference was statistically significant between cervical squamous cancer compared with HSIL, HSIL compared with LSIL(P=0.003, P=0.028); the difference was not statistically significant between LSIL and chronic cervicitis(P=0.654). Expression of Dyrk1 b was correlated with muscular invasion depth of cervical cancer(P<0.05), but not with age,clinical stage, lymph node metastasis, SCC expression and HPV infection(P>0.05). 2. Dyrk1 b protein was expressed in different levels in Hela, Siha or Caski cells, and the expression of Dyrk1 b decreased gradually as the increase of the concentration of AZ191 in Siha and Hela cells for 48 h treatment. 3. Different concentration of AZ191 acting on cervical cancer cells can inhibit the proliferation of cells and dependent on the concentration of inhibitor. As the increase of AZ191 concentration, its effect on the proliferation of cells gradually increased, survival rate of cells in various concentrations was decreased, compared with control group, the difference was statistically significant(P<0.05). 4. AZ191(5μM, 10μM) acting on cervical cancer cell lines for 48 h treatment can induce cell apoptosis on concentration-dependent manner, The apoptosis multiples of cells increase as the increasing of the inhibitor concentration, the difference was statistically significant(P<0.05). Conclusions:Dyrk1b is overexpressed in either specimens or cells of cervical cancer. The expression of Dyrk1 b protein in cervical lesions was increased as the progress of disease. Dyrk1 b inhibitor AZ191 can inhibit cellular proliferation and induce apoptosis in concentration-dependent manner in cervical cancer cells. Therefore, the result is inferred that Dyrk1 b may play an important role in the occurrence and the development of cervical cancer.