姜黄素及其纳米制剂抗肝癌分子机制研究进展

Progress on Molecular Mechanism of Curcumin and Its Nano-preparation Against Liver Cancer

肝脏移植、切除和射频消融术在肝癌中的应用受到一定限制,因此,需要具有特异性和选择性的新药物来提供更好的治疗。姜黄素是一种疏水性多酚,具有广泛的活性,如抗炎、抗菌、抗氧化和抗肿瘤等特性,其纳米制剂对肿瘤细胞具有更强的生长抑制和促凋亡作用。文献检索发现姜黄素抗肝癌分子机制包括通过调控相关微小RNA(miRNA),乙二醛酶1(GLO1),CD133和血管内皮生长因子(VEGF)表达抑制细胞增殖,通过抑制信号转导及转录激活因子3(STAT3)和Yes相关蛋白(YAP)表达诱导细胞凋亡,调控热休克蛋白70(HSP70)/Toll样受体4(TLR4)信号通路,Wnt/β-连环蛋白(β-catenin)和转化生长因子(TGF)/上皮间质转化(EMT)通路,核转录因子-κB(NF-κB)信号通路及核转录因子E2相关因子2(Nrf2)/Kelch样环氧氯丙烷相关蛋白1(Keap1)信号通路,通过抑制p38丝裂原活化蛋白激酶(MAPK)磷酸化,降低Lin28B表达,调控磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路和抑制G蛋白偶联受体81(GPR81)/羟基羧酸受体-1(HCAR-1)表达逆转化疗耐药性。姜黄素纳米制剂主要包括聚合物胶束、脂质体、负载微泡、纳米胶囊和纳米粒,主要通过将姜黄素递送至肝癌细胞内,从而快速释放药物,增强抗肝癌药效并降低正常肝细胞的毒副作用,其机制包括激活死亡受体5(DR5)/含半胱氨酸的天冬氨酸蛋白水解酶(Caspase)介导的外源性凋亡途径和VEGF/VEGF受体(VEGFRs)信号通路,线粒体膜电位损失和增加细胞内活性氧(ROS)等。该文从姜黄素及其纳米制剂抗肝癌分子机制两方面进行总结,以进一步明确肝癌分子机制,为其临床诊治提供新参考。

There are certain limitations in the application of liver transplantation,resection and radiofrequency ablation for liver cancer. Therefore,specific and selective new drugs are needed to provide better treatment. Curcumin is a hydrophobic polyphenol with a wide range of activities,such as anti-inflammatory,antibacterial,anti-oxidant and anti-tumor properties. Its nano-preparation has stronger growth inhibition and proapoptosis effects on tumor cells. Literature retrieval found that curcumin’s anti-liver cancer molecular mechanisms include inhibiting cell proliferation by regulating the expressions of relevant miR,glyoxalase 1(GLO1),CD133 and vascular endothelial growth factor(VEGF),inhibiting signal transducer and activator of transcription(STAT3) and YAP expression to induce cell apoptosis,regulating the heat shock protein 70(HSP70)-Toll-like receptor 4(TLR4)signaling pathway,Wnt/β-catenin and transforming growth factor(TGF)/epithelial-mesenchymal transition(EMT)pathways,nuclear factor-κB(NF-κB)signaling pathway and nuclear factor E2-related factor 2(Nrf2)/Kelch-like ECH-related protein 1(Keap1)signaling pathway,inhibiting p38 mitogen-activated protein kinase(MAPK) phosphorylation, to reduce Lin28 B expression, regulating phosphatidylinositol 3-kinase(PI3 K)/protein kinase B(Akt)signaling pathway and inhibiting G protein-coupled receptors(GPR81)/hydroxycarboxylic acid receptor-1(HCAR-1)expression to reverse transformation therapy resistance. Curcumin nano-preparation mainly includes polymer micelles,liposomes,loaded microbubbles,nanocapsules and nanoparticles. Curcumin is mainly delivered to liver cancer cells to rapidly release the drug,enhance the anti-liver cancer effect and reduce toxic and side effects in normal liver cells. The mechanisms include activation of DR5/Caspase-mediated exogenous apoptosis pathway and VEGF/VEGF receptors(VEGFRs)signaling pathway,loss of mitochondrial membrane potential and increase of intracellular reactive oxygen species(ROS). This paper summarizes the molecular mechanism of curcumin and its nano-preparation against liver cancer,in order to further define the molecular mechanism of liver cancer and provide a new reference for its clinical diagnosis and treatment.