Department of Cell Biology, Key Laboratory of Cell Biology of Ministry of Public Health of China, China Medical University, Shenyang, China.
Cancer Biol Ther. 2009 Jul;8(14):1360-8. doi: 10.4161/cbt.8.14.8720. Epub 2009 Jul 13.
Curcumin (diferuloylmethane), is a natural chemopreventive agent known to inhibit the proliferation of several cancer cell lines. It has been previously demonstrated that curcumin is a potent inhibitor of EGF-receptor (EGFR) tyrosine kinase, but its inhibitive effect on p21-activated kinase 1 (PAK1), a downstream protein of EGFR, has not been defined. In this paper we found that curcumin repressed the expression of HER2 and inhibited the kinase activity of PAK1 without affecting its expression. Silencing HER2 in gastric cancer cells showed that even if PAK1 activity was transiently strengthened by EGF, curcumin still had a strong inhibitive effect. It should be emphasized that kinase assay in vitro showed that curcumin could act as an ATP-competitive inhibitor, which was supported by computer-aided molecular modeling. Curcumin also downregulated the mRNA and the protein expression of cyclin D1 and suppressed transition of the cells from G(1) to S phase. Therefore, curcumin inhibited the proliferation and invasion of gastric cancer cells. Overall, these results provided novel insights into the mechanisms of curcumin inhibition of gastric cancer cell growth and potential therapeutic strategies for gastric cancer.
姜黄素（二芳基甲烷）是一种天然的化学预防剂，已知可抑制多种癌细胞系的增殖。先前已经证明姜黄素是表皮生长因子受体（EGFR）酪氨酸激酶的有效抑制剂，但其对 EGFR 的下游蛋白 p21 激活激酶 1（PAK1）的抑制作用尚未确定。在本文中，我们发现姜黄素可抑制 HER2 的表达并抑制 PAK1 的激酶活性，而不影响其表达。在胃癌细胞中沉默 HER2 表明，即使 PAK1 活性被 EGF 短暂增强，姜黄素仍具有很强的抑制作用。应该强调的是，体外激酶测定表明姜黄素可以作为一种 ATP 竞争性抑制剂，这得到了计算机辅助分子建模的支持。姜黄素还下调了细胞周期蛋白 D1 的 mRNA 和蛋白表达，并抑制了细胞从 G1 期向 S 期的过渡。因此，姜黄素抑制了胃癌细胞的增殖和侵袭。总的来说，这些结果为姜黄素抑制胃癌细胞生长的机制提供了新的见解，并为胃癌的潜在治疗策略提供了依据。
