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异槲皮苷通过丝裂原活化蛋白激酶(MAPK)信号通路在体内和体外抑制肝癌进展。

Isoquercitrin inhibits the progression of liver cancer in vivo and in vitro via the MAPK signalling pathway.

作者信息

Huang Guihong, Tang Bo, Tang Kun, Dong Xiaomin, Deng Jungang, Liao Luqin, Liao Zengzhen, Yang Hua, He Songqing

机构信息

Department of Pharmacy, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi 541001, P.R. China.

Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi 541001, P.R. China.

出版信息

Oncol Rep. 2014 May;31(5):2377-84. doi: 10.3892/or.2014.3099. Epub 2014 Mar 20.

Abstract

Liver cancer is a malignant tumour with high morbidity and fatality rates that is common worldwide. At present, the clinical approaches to treating primary liver cancer include partial hepatectomy, systemic or local chemotherapy, radiotherapy, radiofrequency ablative surgery and liver transplantation. However, all of these approaches have shortcomings, including poor prognosis and numerous side-effects. A large number of studies have proven that many effective ingredients in traditional Chinese medicine, particularly the flavonoid compounds extracted from plants, have achieved breakthroughs in terms of enhancing the effects and reducing the toxicity of chemotherapy and radiotherapy, preventing tumour metastasis and relapse after surgery, alleviating the clinical symptoms of advanced tumours, improving the quality of life of the patient with tumours and extending patient long‑term survival. The purpose of the present study was to investigate the impact of isoquercitrin, the flavonoid from Bidens bipinnata L. extract, on the progression of liver cancer and to achieve a deeper understanding of the biological characteristics of isoquercitrin's involvement in the progression of liver cancer. In the in vitro experiments, isoquercitrin was found to strongly inhibit the proliferation of human liver cancer cells, promote the apoptosis of human liver cancer cells, and block the cell cycle in the G1 phase. Isoquercitrin activated caspase-3, -8 and -9, inhibited the expression level of ERK and p38MAPK protein phosphorylation, and promoted the phosphorylation of JNK. Additionally, isoquercitrin reduced the expression level of PKC in human liver cancer cells. In the in vivo experiments, isoquercitrin was also found to significantly inhibit the growth of transplanted tumours in nude mice. The present study confirmed that isoquercitrin could inhibit the progression of human liver cancer in vivo and in vitro, and the molecular mechanism of isoquercitrin may be closely associated with the MAPK and PKC signalling pathways.

摘要

肝癌是一种在全球范围内发病率和死亡率都很高的恶性肿瘤。目前,原发性肝癌的临床治疗方法包括肝部分切除术、全身或局部化疗、放疗、射频消融手术和肝移植。然而,所有这些方法都有缺点,包括预后不良和大量副作用。大量研究证明,中药中的许多有效成分,特别是从植物中提取的黄酮类化合物,在增强化疗和放疗效果、降低毒性、预防术后肿瘤转移和复发、缓解晚期肿瘤的临床症状、提高肿瘤患者的生活质量以及延长患者长期生存期方面取得了突破。本研究的目的是探讨来自鬼针草提取物的黄酮类化合物异槲皮苷对肝癌进展的影响,并更深入地了解异槲皮苷参与肝癌进展的生物学特性。在体外实验中,发现异槲皮苷强烈抑制人肝癌细胞的增殖,促进人肝癌细胞的凋亡,并将细胞周期阻滞在G1期。异槲皮苷激活了caspase-3、-8和-9,抑制了ERK和p38MAPK蛋白磷酸化的表达水平,并促进了JNK的磷酸化。此外,异槲皮苷降低了人肝癌细胞中PKC的表达水平。在体内实验中,还发现异槲皮苷显著抑制裸鼠移植瘤的生长。本研究证实,异槲皮苷在体内和体外均可抑制人肝癌的进展,其分子机制可能与MAPK和PKC信号通路密切相关。

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