Effects of125I-labeled peptide nuclear acid targeting Ki67 on the growth of implanted human renal cell carcinoma in nude mice
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To investigate the potential of125I-labeled anti-sense peptide nucleic acids (125I-AS-PNAs) to inhibit the expression of the Ki-67 gene and growth of implanted human renal carcinoma cells in nude mice.
Anti-sense peptide nucleic acids (AS-PNAs) targeting the Ki67 gene were synthesized and labeled with125I by the Chloraseptine-T method. Drugs including PNAs and125I-AS-PNAs capsulated by cationic lipid were directly injected into tumors in nude mice. The Ki67 expression in tumors was detected by an immunohistochemical technique and Western blot. The apoptosis of tumor cells was detected by a TUNEL assay. Tumor volumes were measured every 3 days and tumor suppression rates were calculated at 12 days after treatment. Control groups were treated with AS-PNA, MM-PNAs (mismatch PNAs) and125l-Na.
The Ki67 expression rate of tumors treated by125I-AS-PNAs [( 15.3±1.8)%] was lower than that treated by AS-PNAs [(23.0±2.4)%] (P< 0.01). The Ki67 protein production rate of tumors treated by125I-AS-PNAs [(43.6±3.5)%] was lower than that treated by AS-PNAs [(59.7±2.3)%] (P< 0.01). The apoptosis rate of tumors treated by125I-AS-PNAs [(40.3±2.4)%] was higher than that treated by AS-PNAs [(31.1 ±2.0)%] (P< 0.01). The volume of tumors treated by125l-AS-PNAs [(330.4±57.8) mm3 ]was smaller than that treated by AS-PNAs[(513.2±64.2)mm3] (P< 0.01).
125I-AS-PNAs targeted against the Ki67 gene have a greater inhibitory effect on the expression of the Ki67 gene and a larger apoptotic action on human renal carcinoma cells and can more efficiently inhibit tumor growth than AS-PNAs.125I-AS-PNAs targeting the Ki67 gene may be a promising anti-sense/anti-gene radiotherapy method for treating renal cell carcinoma.
Keywordspeptide nucleic acids Ki67 gene gene radiotherapy radionuclide renal cell carcinoma apoptosis
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- 3.Zheng JN, Sun XQ, Chen JC, et al. Effects of125I-labeled Ki67 gene targeting peptide nucleic acids on the proliferation and apoptosis of human renal carcinoma cell line. Chin J Nuclear Med. 2004;24:139–141.Google Scholar