Therapeutic effects of radioisotope labeled Ku70 antisense oligodeoxynuclecotide on thyroid carcinoma implanted in nude mice
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    Abstract:

    ObjectiveTo investigate the therapeutic effects of radioisotope labeled Ku70 antisense oligodeoxynuclecotide (ASODNs) on thyroid carcinoma implanted in nude mice and the related mechanism. MethodsThe 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). AnnexinⅤ/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). ResultsAfter 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. ConclusionThe 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.

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History
  • Received:July 07,2010
  • Revised:December 08,2010
  • Adopted:December 17,2010
  • Online: January 20,2011
  • Published:
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