5-氮杂-2'-脱氧胞苷对人甲状腺癌裸鼠移植瘤的 抑制作用及其机制的研究.

Objective To observe the inhibitory effect of 5-aza-2'-deoxycytidine (5-Aza-CdR) on the growth of human papillary thyroid carcinoma TPC-1 cells in nude mice. Methods Human papillary thyroid carcinoma TPC-1 cells were inoculated subcutaneously under the armpit of right forelimb in 16 female BALB/ C nude mice. After the model was established, the nude mice were divided into 2 groups. The experimental group was intraperitoneally injected with 5-AzaCdR 200 μL per 1 μg/g, and the control group was intraperitoneally injected with iso-volume sterile normal saline, once every 2 days for 4 weeks. The tumor-bearing mice were killed after the last drug intervention. The growth of transplanted tumors in nude mice of the two groups was observed. The histopathological changes of transplanted tumors were observed by HE staining. Methylation-specific PCR was used to detect the methylation degree of death associated protein kinase (DAPK) gene, and the protein expression levels of DAPK and DNA methyltransferases (DNMTs) were detected by immunohistochemical staining and Western blot assay. Results After 4 weeks of drug intervention, the tumor volume and weight were significantly reduced in the experimental group compared with the control group (P＜0.05), and the tumor inhibition rate was 45.38% in the experimental group compared with the control group. HE staining results showed that the number of tumor cells in the experimental group was reduced, the nuclei of tumor in some areas were faint and shrunken, and nuclear pyknosis and nucleolysis occurred locally. DAPK gene methylation was lower in the experimental group than that in the control group. Immunohistochemical staining and Western blot results showed that the expression of DAPK protein was significantly higher in the experimental group than that in the control group, while the expression levels of DNMT1 and DNMT3A protein were significantly lower than those in the control group (P＜0.05). There was no significant difference in the expression of DNMT3B between the two groups (P＞0.05). Conclusion 5-Aza-CdR can increase the expression of DAPK by regulating DNMTs in transplanted tumor of nude mouse, thus inhibiting the growth of antithyroid papillary carcinoma. [ABSTRACT FROM AUTHOR]