Curcumol Inhibits Growth and Induces Apoptosis of Colorectal Cancer LoVo Cell Line via IGF-1R and p38 MAPK Pathway.
Curcumol Inhibits Growth and Induces Apoptosis of Colorectal Cancer LoVo Cell Line via IGF-1R and p38 MAPK Pathway.
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姜黄酚通过 IGF-1R 和 p38 MAPK 通路抑制结直肠癌 LoVo 细胞系生长并诱导细胞凋亡
DOI：
10.3390/ijms160819851
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发表时间：
2015-08-20
影响因子：
5.6
通讯作者：
Chen X
中科院分区：
文献类型：
--
作者：
Wang J;Huang F;Bai Z;Chi B;Wu J;Chen X
姜黄醇是从传统药用植物郁金中分离得到的活性成分，其潜在的抗肿瘤作用近年来引起了人们的广泛关注。虽然许多研究人员已经报道了姜黄醇及其生物活性，但其在结直肠癌LoVo细胞中抗癌作用的潜在分子机制仍不清楚。在本研究中，我们发现姜黄醇以剂量和时间依赖的方式抑制LoVo细胞的生长并诱导其凋亡。其增殖抑制和细胞凋亡的发生伴随着IGF-1R表达的抑制，进而上调p38丝裂原活化蛋白激酶(MAPK)的磷酸化，可能通过抑制CREB生存通路而引起级联反应，最终触发Bax/Bcl-2和多聚ADP-核糖聚合酶1(PARP-1)的凋亡信号。此外，姜黄醇还能抑制裸鼠移植瘤模型中的结直肠癌。免疫组织化学和Western印迹分析显示，姜黄醇可降低Ki-67、Bcl-2和CREB1的表达，增加Bax的表达和p38的磷酸化，这与我们的体外实验结果一致。总之，我们的体外和体内实验数据证实了姜黄醇的抗癌活性，这与其显著抑制IGF-1R和激活p38MAPKs有关，表明姜黄醇可能是一种潜在的结直肠癌治疗药物。
Curcumol, isolated from the traditional medical plant Rhizoma Curcumae, is the bioactive component of Zedoary oil, whose potential anti-tumor effect has attracted considerable attention in recent years. Though many researchers have reported curcumol and its bioactivity, the potential molecular mechanism for its anti-cancer effect in colorectal cancer LoVo cells still remains unclear. In the present study, we found that curcumol showed growth inhibition and induced apoptosis of LoVo cells in a dose- and time-dependent manner. The occurrence of its proliferation inhibition and apoptosis came with suppression of IGF-1R expression, and then increased the phosphorylation of p38 mitogen activated protein kinase (MAPK), which might result in a cascade response by inhibiting the CREB survival pathway and finally triggered Bax/Bcl-2 and poly(ADP-ribose) polymerase 1 (PARP-1) apoptosis signals. Moreover, curcumol inhibited colorectal cancer in xenograft models of nude mice. Immunohistochemical and Western blot analysis revealed that curcumol could decrease the expression of ki-67, Bcl-2 as well as CREB1, and increase the expression of Bax and the phosphorylation of p38, which were consistent with our in vitro study. Overall, our in vitro and in vivo data confirmed the anti-cancer activity of curcumol, which was related to a significant inhibition of IGF-1R and activation of p38 MAPKs, indicating that curcumol may be a potential anti-tumor agent for colorectal carcinoma therapy.