Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling.
Curcumin inhibits cancer-associated fibroblast-driven prostate cancer invasion through MAOA/mTOR/HIF-1α signaling.
复制标题
姜黄素通过 MAOA/mTOR/HIF-1 α 信号传导抑制癌症相关成纤维细胞驱动的前列腺癌侵袭
DOI：
10.3892/ijo.2015.3202
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发表时间：
2015-12
影响因子：
5.2
通讯作者：
He D
中科院分区：
文献类型：
--
作者：
Du Y;Long Q;Zhang L;Shi Y;Liu X;Li X;Guan B;Tian Y;Wang X;Li L;He D
癌症相关成纤维细胞（CAF）是癌症恶性进展的关键决定因素，支持肿瘤发生和转移。CAF还介导肿瘤细胞中的上皮向间充质转化（EMT）及其干细胞性状的实现。姜黄素最近被发现通过其对参与癌症进展的多种生物学途径的作用而具有抗癌活性。本研究发现CAFs可通过单胺氧化酶A（MAOA）/哺乳动物雷帕霉素靶蛋白（mTOR）/缺氧诱导因子-1 α（HIF-1α）信号通路诱导前列腺癌细胞EMT和侵袭，该信号通路利用活性氧（ROS）驱动前列腺癌细胞的迁移和侵袭表型。此外，CAFs能够增加前列腺癌细胞中CXC趋化因子受体4（CXCR 4）和白细胞介素-6（IL-6）受体的表达。然而，姜黄素通过抑制MAOA/mTOR/HIF-1α信号通路，抑制前列腺癌细胞的ROS产生和CXCR 4、IL-6受体表达，从而抑制CAF诱导的侵袭和EMT，支持姜黄素对前列腺癌的治疗作用。
Cancer-associated fibroblasts (CAFs) are key determinants in the malignant progression of cancer, supporting tumorigenesis and metastasis. CAFs also mediate epithelial to mesenchymal transition (EMT) in tumor cells and their achievement of stem cell traits. Curcumin has recently been found to possess anticancer activities via its effect on a variety of biological pathways involved in cancer progression. In this study, we found that CAFs could induce prostate cancer cell EMT and invasion through a monoamine oxidase A (MAOA)/mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway, which exploits reactive oxygen species (ROS) to drive a migratory and aggressive phenotype of prostate carcinoma cells. Moreover, CAFs was able to increase CXC chemokine receptor 4 (CXCR4) and interleukin-6 (IL-6) receptor expression in prostate cancer cells. However, curcumin abrogated CAF-induced invasion and EMT, and inhibited ROS production and CXCR4 and IL-6 receptor expression in prostate cancer cells through inhibiting MAOA/mTOR/HIF-1α signaling, thereby supporting the therapeutic effect of curcumin in prostate cancer.