沉默PAK6基因可抑制前列腺癌生长并增强多烯紫杉醇的作用

Knock-down of PAK6 expression inhibits prostate cancer growth and enhances chemosensitivity to docetaxel

目的观察沉默p21活化激酶6（PAK6）基因对前列腺癌生长及联用多烯紫杉醇的作用。方法转染siRNA（30nmol／L）前列腺癌细胞PC-3和DU145中，检测细胞增殖、集落形成能力、侵袭性能力、细胞周期及凋亡。以3×10^6个PC-3细胞（100μl）注射裸鼠皮下成瘤，观察siRNA及联用多烯紫杉醇对肿瘤生长效应。结果PAK6-siRNA能有效沉默PAK6并抑制前列腺癌细胞的生长、集落形成能力和侵袭力、使细胞周期停滞在G2／M期。还可抑制裸鼠体内移植瘤生长。PAK6-siRNA治疗组瘤体重为（146．0±8．5）mg，低于对照组（451．0±22．3）mg（P〈0．01）。PAK6-siRNA在体内外均可增强多烯紫杉醇作用。结论沉默PAK6可抑制前列腺癌生长并增强多烯紫杉醇的化疗作用。

Objective To evaluate the effect of silencing p21-activated kinase 6 （PAK6） gene on the growth of prostate cancer and the efficiency of combined use of docetaxel. Methods PAK6 in PC- 3 and DU145 prostate cancer cells was knocked down by small interfering RNA （siRNA, 30 nmol/L）. Cellular proliferation, cell cycle, apoptosis, colony forming capacity and invasive ability were tested. PC-3 cells （3 × 10^6/100 μl） were injected into nude mice and xenograft tumor was formed. The in vivo growth of tumor which was treated with PAK6-siRNA or in combination with docetaxel was examined. Results PAK6-siRNA efficiently down-regulated PAK6 and inhibited cell growth. It also suppressed cell colony forming capacity in soft agar, invasive ability, and caused cell cycle arrest in G2/M phase. Xenograft tumor growth in nude mice was inhibited significantly by PAK6-siRNA. The weight of the harvested tumor in the siRNA group was （ 146.0 ± 8.5） mg,which was less than the （451.0 ± 22.3 ） mg in the control group （ P 〈 0.01 ）. Combined used of PAK6-siRNA and docetaxel produced a greater effect than docetaxel alone in both in vitro and in vivo models. Conclusion Knock-down of PAK6 inhibits prostate cancer growth and enhances chemosensitivity to docetaxel.