Ras inhibition results in growth arrest and death of androgen-dependent and androgen-independent prostate cancer cells
Ras inhibition results in growth arrest and death of androgen-dependent and androgen-independent prostate cancer cells
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DOI：
10.1016/j.bcp.2006.05.007
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发表时间：
2006-08-14
影响因子：
5.8
通讯作者：
Pinkas-Kramarski, Ronit
中科院分区：
文献类型：
--
作者：
Erlich, Shlomit;Tal-Or, Pazit;Pinkas-Kramarski, Ronit
前列腺癌是人类男性中最常诊断的癌症之一。这些肿瘤的进展是由自分泌/副分泌生长因子促进的，其激活促进前列腺癌细胞生长、存活和迁移的关键信号级联。其中，Ras途径具有重要作用。我们研究了Ras抑制剂S-反式法尼基硫代水杨酸（FTS）对雄激素依赖性和雄激素非依赖性前列腺癌细胞生长和活力的影响，FTS下调LNCaP和PC 3细胞中Ras，抑制Akt信号转导，降低细胞周期调控蛋白cyclin D1、p-RB、E2 F-1和cdc 42的水平。因此，LNCaP和PC 3细胞的贴壁依赖性和非贴壁依赖性生长均受到抑制。FTS还诱导细胞凋亡，这是抑制的广谱半胱天冬酶抑制剂，Boc-asp-FMK。我们的研究表明，雄激素依赖性和雄激素非依赖性前列腺癌细胞的生长和存活需要活性Ras。FTS抑制Ras导致生长停滞和细胞死亡。FTS可作为治疗前列腺癌的潜在药物。(c)2006年爱思唯尔公司All rights reserved.
Prostate cancer is one of the most frequently diagnosed cancers in human males. Progression of these tumors is facilitated by autocrine/parachne growth factors which activate critical signaling cascades that promote prostate cancer cell growth, survival and migration. Among these, Ras pathways have a major role. Here we examined the effect of the Ras inhibitor S-trans, trans-farnesylthiosalicylic acid (FTS), on growth and viability of androgen-dependent and androgen-independent prostate cancer cells.FTS downregulated Ras, inhibited signaling to Akt and reduced the levels of cell-cycle regulatory proteins including cyclin D1, p-RB, E2F-1 and cdc42 in LNCaP and PC3 cells. Consequently the anchorage-dependent and anchorage-independent growth of LNCaP and PC3 cells were inhibited. FTS also induced apoptotic cell death which was inhibited by the broad-spectrum caspases inhibitor, Boc-asp-FMK. Our study demonstrated that androgen-dependent and androgen-independent prostate cancer cells require active Ras for growth and survival. Ras inhibition by FTS results in growth arrest and cell death. FTS may be qualified as a potential agent for the treatment of prostate cancer. (c) 2006 Elsevier Inc. All rights reserved.