Therapeutic effects of radioisotope labeled Ku70 antisense oligodeoxynuclecotide on thyroid carcinoma implanted in nude mice / 第二军医大学学报

ABSTRACT

Objective: To investigate the therapeutic effects of radioisotope labeled Ku70 antisense oligodeoxynuclecotide (ASODNs) on thyroid carcinoma implanted in nude mice and the related mechanism. Methods: The Ku70 ASODNs labeled with 131I was used to treat the tumor-bearing mouse model derived from thyroid carcinoma TT cells. The tumor-forming rate, mortality rate and tumor growth were observed and calculated after treatment with 131I-ASODNs, 131I-Na, ASODNs or NS (normal saline). Annexin V/PI assay was used to examine the apoptosis of tumor cells by flow cytometry. Western blotting analysis was performed to determine the protein expressions of Ku70, proliferating cell nuclear antigen (PCNA, a cell proliferation marker) and Bcl-2(a cell apoptosis marker). Results: After treatment with 131I-ASODNs, the Ku70 protein level was down-regulated in the tumor tissues and the growth of tumor was inhibited. The tumor volume, tumor-forming rate and mortality rate were significantly decreased in 131I-ASODNs group than in the NS control group (P<0.01). The tumor volume of 131I-ASODNs group was also significantly smaller than that in the 131I-Na group (P<0.05); the apoptosis rate of 131I- ASODNs group (35.6%) was significantly higher than that of the ASODNs group (10.4%), NS group (9.2%) and 131I-Na group (26.6%) (P<0.05). Further investigation found that PCNA and Bcl-2 protein levels in 131I-ASODNs group were lower than those in NS and ASODNs groups. Conclusion: The Ku70 131I-ASODNs can effectively inhibit the growth of thyroid carcinoma and promote apoptosis of TT tumor cells, which might be related to the down-regulation of Ku70 and the changes of PCNA and Bcl-2 signal pathway.