利用中藥治療癌癥并不是什么新聞,著名的砒霜就是治療白血病的一種有效中藥,,近年來(lái)不少研究組展開(kāi)了利用天然中草藥治療癌癥的研究,,近期來(lái)自中國(guó)藥科大學(xué),,天然藥物活性組分與藥效國(guó)家重點(diǎn)實(shí)驗(yàn)室等處的研究人員就發(fā)現(xiàn)了一種古老的中藥:黃芩的主要成分能通過(guò)作用于一種關(guān)鍵酶,,影響AML癌細(xì)胞的增殖,,并指出這一成分也許能用于A(yíng)ML癌癥治療,。相關(guān)研究成果公布在3月《血液》(Blood)雜志上,。
領(lǐng)導(dǎo)這一研究的是中國(guó)藥科大學(xué)郭青龍教授,郭青龍教授主要從事腫瘤的發(fā)病機(jī)制及抗腫瘤藥的發(fā)現(xiàn)性研究,,近幾年發(fā)表研究論文100余篇,,SCI收載80余篇,總引用次數(shù)達(dá)到600余次,,此前曾在腦膠質(zhì)瘤發(fā)病機(jī)制研究方面獲得新的發(fā)現(xiàn),。
漢黃芩苷(Wogonoside)是從中藥黃芩(Scutellaria baicalensis Georgi)中提取的主要黃酮類(lèi)成分,黃芩是一種古老的中草藥,,李時(shí)珍在《本草綱目》中曾自述說(shuō),,他20歲那年,因患感冒咳嗽,,骨蒸發(fā)熱,,肌膚如火燎一樣熱,盡管用了柴胡,、麥冬等藥都不見(jiàn)好,,他父親單用黃芩一兩煎湯,讓李時(shí)珍服下,,很快病情就得到了好轉(zhuǎn),。因此黃芩被認(rèn)為具有清熱燥濕等功效。
在這項(xiàng)研究中,,研究人員分析了漢黃芩苷對(duì)急性髓系白血病(AML)的治療作用,,他們針對(duì)AML細(xì)胞系和來(lái)自患者的AML細(xì)胞展開(kāi)了研究,,發(fā)現(xiàn)漢黃芩苷在體外和體內(nèi)都表現(xiàn)出了抗細(xì)胞增殖的特性。而且這種成分能通過(guò)誘導(dǎo)G1期阻滯和促進(jìn)分化,,有效抑制U937和HL-60細(xì)胞的增殖,。
此外這項(xiàng)研究還表明,,漢黃芩苷能顯著增加磷脂爬行酶1(phospholipid scramblase 1,PLSCR1)的轉(zhuǎn)錄,,這是由漢黃芩苷對(duì)細(xì)胞周期和分化相關(guān)基因的影響而導(dǎo)致的,,這些影響包括促進(jìn)p21cip的表達(dá),以及抑制c-Myc基因的表達(dá),。
漢黃芩苷也能促進(jìn)PLSCR1進(jìn)入細(xì)胞核,,結(jié)合到1,4,5-三磷酸肌醇受體1(IP3R1)的啟動(dòng)子上,從而增加了IP3R1的表達(dá),。并且研究人員還通過(guò)RNA干擾抑制PLSCR1的表達(dá),,發(fā)現(xiàn)這能部分阻斷漢黃芩苷誘導(dǎo)細(xì)胞周期阻滯和分化,擾亂漢黃芩苷相關(guān)的分子事件,。
因此,,研究人員認(rèn)為這項(xiàng)研究結(jié)果表明,漢黃芩苷可以作為AML治療中的一種候選藥物,。
近期瑞金醫(yī)院的陳竺陳賽娟院士研究組也發(fā)現(xiàn)了一種萜類(lèi)化合物:毛萼乙素(Eriocalyxin B,,EriB)能通過(guò)靶向關(guān)鍵信號(hào)通路,選擇性調(diào)控Th1和Th17細(xì)胞,,發(fā)揮強(qiáng)有力的抗炎作用,,這不僅有助于癌癥治療的研發(fā),也為自身免疫疾病的治療,,也提出了一種獨(dú)特的治療方向,。(生物谷Bioon.com)
doi:10.1182/blood-2012-11-466219
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Wogonoside induces cell cycle arrest and differentiation by affecting expression and subcellular localization of PLSCR1 in AML cells
Yan Chen, Hui Hui, Hao Yang, Kai Zhao, Yansu Qin, Cong Gu, Xiaotang Wang
Wogonoside is the main flavonoid component derived from the root of Scutellaria baicalensis Georgi. It is a popular Chinese herbal medicine with the potential to treat hematologic malignancies. In this study, we investigated the anti-cancer effects of wogonoside in acute myeloid leukemia (AML) cell lines and primary patient-derived AML cells. Wogonoside exerted anti-proliferative properties both in vitro and in vivo. Furthermore, it efficiently inhibited the proliferation of U937 and HL-60 cells through induction of G1 phase arrest and promotion of differentiation. We also demonstrated that wogonoside significantly increased the transcription of phospholipid scramblase 1 (PLSCR1) due to its influence on the expression of cell cycle- and differentiation-related genes, including up-regulation of p21cip and down-regulation of c-Myc. Wogonoside also promoted PLSCR1 trafficking into the nucleus and facilitated its binding to the inositol 1, 4, 5-trisphosphate receptor 1 (IP3R1) promoter, thus increasing the expression of IP3R1. Finally, inhibition of PLSCR1 expression with small interfering RNA partially blocked wogonoside-induced cell cycle arrest and differentiation and disturbed the wogonoside-associated molecular events. The results of this study therefore suggest that wogonoside may represent a therapeutic candidate for the treatment of AML.