Study of Histone Deacetylase on the Target Therapy of Uterine Cervical Cancers
|Course||Pathology and Pathophysiology|
|Keywords||Histone Deacetylase Cervical Cancer Short interfering RNA Immunohistochemistry Immunofluorescence staining Western Blot|
Objective: To investigate the histone deacetylase (Histone deacetylase, HDAC) gene and its protein expression the clinicopathological significance to detect cervical cancer and precancerous lesions and HDAC inhibitor trichostatin A (Trichostatin A, the TSA role) in cervical cancer molecular targeted therapy. Materials and Methods: 8 cases of normal cervical squamous epithelium, 52 cases of cervical intraepithelial the neoplasia (Cervicalintraepithelial neoplasia, CIN), 141 cases of cervical squamous cell carcinoma (Squamous cellcarcinomas, SCC) and 24 cases of cervical adenocarcinoma (Adenocarcinomas, AC ) a total of 225 cases of cervical lesions archived paraffin block specimens selected from the group consisting of Yanbian University Hospital, Yanbian Maternal and Child Health Hospital and Korea University Medical University Medical Center, Department of Pathology. At the same time, select two cervical cancer cell line HeLa and CaSki XTT detect objects as TSA in vitro treatment effect. Immunohistochemistry, immunofluorescence and Western Blot experimental methods to detect changes in the expression of the five kinds of the HDAC gene protein in normal cervical epithelium, CIN and cervical cancer, and application of small molecule RNA interference, XTT and flow cytometry methods HDACs inhibitor TSA for cervical cancer cell killing effect and mechanism. Results: HDAC1, 3 and HDAC5 protein mainly to the nucleus positive expression in normal cervical epithelium were 0 (0/8), 12.5% ??(1/8) and 25% (2/8), and positive cells located in the basal cell layer of the epithelium, but expression was significantly increased in CIN, cervical squamous cell carcinoma and adenocarcinoma. HDAC1 in CIN, cervical squamous cell carcinoma and adenocarcinoma positive rate were 82.7% (43/50), 83% (117/141) and 91.7% (22/24); HDAC3 in CIN, cervical squamous cell carcinoma and adenocarcinoma The positive rate was 58.7% (27/46), 62.4% (87/141) and 70.8% (17/24);-positive rate of HDAC5 in CIN, cervical squamous cell carcinoma and adenocarcinoma were 66% (33 / 50), 63.1% (89/141) and 75% (18/24). HDAC6 showed cytoplasmic positive expression in normal cervical epithelium was 0 (0/8), and the distribution of weakly positive staining cells in the basal cells of the epithelial layer; expression in CIN, SCC and adenocarcinoma also significantly increased, respectively, 84.6% (44/52), 83.0% (117/141) and 91.7% (22/24). HDAC2 protein expression in normal cervical epithelial tissue was negative, but also weak expression in cervical cancer and precancerous lesions in only a few cases showed HDAC2 protein positive. The TSA for HeLaCaSki cervical cancer cells killing role, but normal skin squamous cell TSA is not sensitive. TSA treated HeLa cell apoptosis and mortality significantly compared with HeLa control group of untreated high Acetylated Tubulin (acetylated tubulin) expression levels were significantly increased. Conclusion: HDAC1, 3,5 and HDAC6 protein detection with auxiliary significance for the diagnosis of cervical cancer, but also can be used as a new target for cervical cancer treatment. At the same time, HDAC inhibitors TSA for cervical cancer killing effect, its mechanism is mainly raised Acetylated tubulin and induction of apoptosis.