目的： 探讨双氢睾酮(dihydrotestosterone，DHT)耦联 Ki67多肽核酸(peptide nucleic acids，PNAs)对激素非依赖性前列腺癌PC3细胞 Ki67 表达、细胞生长及凋亡的影响 方法： 人工合成针对 Ki67 基因的多肽核酸并与DHT耦联(DHTPNAs)后转染PC3细胞,采用RTPCR、免疫细胞化学、Western blotting检测PC3细胞Ki67抗原的表达，CCK8法检测PC3细胞增殖，原位末端标记法（TUNEL）检测PC3细胞凋亡，以上实验均以以PNAs组、DHT组为对照组。 结果： DHTPNAs、PNAs均能抑制非激素依赖性前列腺癌细胞系PC3的 Ki67 表达，诱导PC3细胞凋亡，使细胞生长受抑，并且均具有浓度依赖性。DHTPNAs作用强度明显强于相同剂量的PNAs，3 μmol/L DHTPNAs即可达到9 μmol/L PNAs的作用强度。 结论： DHTPNAs能有效增强PNAs阻抑PC3细胞Ki67表达、诱导细胞凋亡及抑制细胞生长的作用。

Objective:To investigate the effects of Ki67targeting peptide nucleic acids (PNAs) linked with dihydrotestosterone (DHT) on the Ki67 expression, proliferation and apoptosis of hormoneindependent prostate cancer cell line PC3. Methods: Ki67targeting PNAs were artificially synthesized and were covalently linked to DHT to yield DHTPNAs. DHTPNAs were then transfected into PC3 cells. Ki67 expression in PC3 cells was examined by RTPCR, immunohistochemistry and Western blotting assay. The proliferation of PC3 cells was examined by CCK8 assay, and the apoptosis of PC3 cells was detected by TUNEL assay. Groups treated with PNAs or DHT served as controls. Results: Both PNAs and DHTPNAs inhibited the expression of Ki67 in PC3 cells, increased the apoptotsis of PC3 cells, and inhibited the proliferation of PC3 cells in a dosedependent manner. The therapeutic effect of DHTPNAs at the same concentration was better than that of PNAs, with 3 μmol/L DHTPNAs (onethird of PNAs dose) reaching the same therapeutic effect of PNAs.Conclusion: DHTPNAs can promote the effects of PNAs in inhibiting Ki67 expression, inducing apoptosis and inhibiting proliferation of PC3 cells.

广东省医学科学研金基金资助课题(No.A2005805)