Chen Quan, Li Ping, Li Ping, Xu Yong, Li Yang, Tang Bo
Department of Anesthesiology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
Department of Oncology, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
Oncol Rep. 2015 Feb;33(2):840-8. doi: 10.3892/or.2014.3626. Epub 2014 Nov 26.
Pancreatic cancer is a common malignant tumour that affects individuals worldwide. In recent years, the incidence and mortality rates of pancreatic cancer have continuously increased. Currently, the primary clinical treatment methods for pancreatic cancer include surgical resection, chemotherapy and radiotherapy. However, these treatment methods rarely produce satisfactory therapeutic outcomes. Extensive research has also proven that the effective components of several traditional Chinese medicines, particularly flavonoids extracted from plants, have significant antitumour effects. Isoquercitrin, which is one of the flavonoids found in Bidens pilosa extracts, has a significant antitumour effect. However, the antitumour effect of isoquercitrin and its mechanism of action remain unclear. The objective of the present study was to investigate the effect of isoquercitrin on the progression of pancreatic cancer and to further understand the biological characteristics of the participation of isoquercitrin in the progression of pancreatic cancer. In vitro, we found that a therapeutic dose of isoquercitrin significantly inhibited proliferation, promoted apoptosis and induced cell cycle arrest within the G1 phase in pancreatic cancer cells. Isoquercitrin activated caspase-3, -8 and -9 and reduced the mitochondrial membrane potential. In addition, isoquercitrin inhibited the expression level of the δ opioid receptor; however, isoquercitrin had no effect on the κ and µ opioid receptors. Furthermore, isoquercitrin inhibited extracellular signal-regulated kinase (ERK) phosphorylation and promoted c-Jun N-terminal kinase (JNK) phosphorylation. In vivo, we found that a therapeutic dose of isoquercitrin significantly inhibited xenograft growth in nude mice. In summary, the present study demonstrated that isoquercitrin inhibits human pancreatic cancer progression in vivo and in vitro and that its molecular mechanism may be closely related to opioid receptors and to the activation of the mitogen-activated protein kinase (MAPK) signalling pathway.
胰腺癌是一种影响全球人群的常见恶性肿瘤。近年来，胰腺癌的发病率和死亡率持续上升。目前，胰腺癌的主要临床治疗方法包括手术切除、化疗和放疗。然而，这些治疗方法很少能产生令人满意的治疗效果。广泛的研究还证明，几种中药的有效成分，特别是从植物中提取的黄酮类化合物，具有显著的抗肿瘤作用。异槲皮苷是鬼针草提取物中发现的黄酮类化合物之一，具有显著的抗肿瘤作用。然而，异槲皮苷的抗肿瘤作用及其作用机制尚不清楚。本研究的目的是探讨异槲皮苷对胰腺癌进展的影响，并进一步了解异槲皮苷参与胰腺癌进展的生物学特性。在体外，我们发现治疗剂量的异槲皮苷显著抑制胰腺癌细胞的增殖，促进细胞凋亡并诱导细胞周期停滞在G1期。异槲皮苷激活了caspase-3、-8和-9，并降低了线粒体膜电位。此外，异槲皮苷抑制了δ阿片受体的表达水平；然而，异槲皮苷对κ和μ阿片受体没有影响。此外，异槲皮苷抑制细胞外信号调节激酶（ERK）磷酸化并促进c-Jun氨基末端激酶（JNK）磷酸化。在体内，我们发现治疗剂量的异槲皮苷显著抑制裸鼠异种移植瘤的生长。总之，本研究表明异槲皮苷在体内和体外均能抑制人胰腺癌的进展，其分子机制可能与阿片受体以及丝裂原活化蛋白激酶（MAPK）信号通路的激活密切相关。
