Knockdown of p21-activated Kinase 6 Inhibits Prostate Cancer Growth and Enhances Chemosensitivity to Docetaxel
Knockdown of p21-activated Kinase 6 Inhibits Prostate Cancer Growth and Enhances Chemosensitivity to Docetaxel
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DOI：
10.1016/j.urology.2008.09.041
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发表时间：
2009-06-01
期刊：
影响因子：
2.1
通讯作者：
Gao, Xin
中科院分区：
文献类型：
--
作者：
Wen, Xingqiao;Li, Xiaojuan;Gao, Xin
研究p21激活激酶6（PAK 6）沉默是否会抑制前列腺癌生长，并评估PAK 6沉默与多西他赛联合使用时的作用。PAK 6是一种丝氨酸/苏氨酸激酶，属于PAK家族，并已牵连在细胞运动，凋亡，和transformation.METHODS PAK 6在PC-3，DU 145，和LAPC 4前列腺癌细胞系的表达被敲低的小，干扰RNA（siRNA）。通过基质胶评价细胞增殖、细胞周期分布、凋亡能力和侵袭能力。此外，我们还检测了PAK 6-siRNA单独或联合多西他赛治疗的裸鼠前列腺癌的体内生长情况。PAK 6-siRNA能特异性下调PAK 6的表达，抑制前列腺癌细胞的生长。它还抑制基质胶的侵袭能力，并导致细胞周期停滞在G（2）/M期。PAK 6-siRNA显著抑制裸鼠异种移植瘤的生长。在PAK 6-siRNA组中，收获的肿瘤的平均重量为46 +/- 8.5 mg，低于对照组的451 +/- 22.3 mg（P
OBJECTIVES To investigate whether silencing of p21-activated kinase 6 (PAK6) would inhibit prostate cancer growth and to assess the effect of PAK6 silencing when used in combination with docetaxel. PAK6 is a serine/threonine kinase belonging to the PAK family and has been implicated in cell motility, apoptosis, and transformation.METHODS Expression of PAK6 in PC-3, DU145, and LAPC4 prostate cancer cell lines was knocked down by small, interfering RNA (siRNA). Cellular proliferation, cell cycle distribution, the ability to undergo apoptosis, and the invasive capacity through matrigel were evaluated. Furthermore, in vivo growth of prostate cancer in nude mice treated with PAK6-siRNA alone or in combination with docetaxel was examined.RESULTS PAK6 was overexpressed in prostate cancer tissues. PAK6-siRNA efficiently and specifically downregulated the expression of PAK6 and inhibited cell growth of prostate cancer. It also suppressed invasive ability in matrigel and caused cell cycle arrest at the G(2)/M phase. Xenograft tumor growth in nude mice was inhibited significantly by PAK6-siRNA. The average weight of the harvested tumor was 46 +/- 8.5 mg in the PAK6-siRNA group, lower than the 451 +/- 22.3 mg in the control group (P