中草藥單體石蒜堿和藥根堿的抗黑色素瘤新生血管形成作用及其機(jī)制
發(fā)布時(shí)間：2018-08-02 18:31
【摘要】：黑色素瘤是一種嚴(yán)重危害人類健康的惡性腫瘤，近幾年其發(fā)病率和死亡率都急劇上升，是腫瘤發(fā)病率增長最快的一種。但目前人們對于惡性黑色素瘤的發(fā)病機(jī)理尚不清楚，亦缺乏有效藥物；已有的抗黑色素瘤中草藥療效不佳，需發(fā)掘新的更有效抗癌中草藥。我們以腫瘤細(xì)胞為模型，從120多種中草藥中篩選出兩種抗黑色素瘤效果比較好的中草藥石蒜和黃連，繼而對石蒜的單體鹽酸石蒜堿（LH）和黃連的單體鹽酸藥根堿（JH）的抗黑色素瘤血管形成作用，進(jìn)行了深入研究。發(fā)現(xiàn)兩者對人黑色素瘤C8161細(xì)胞主導(dǎo)的新生血管形成具有很好的抑制作用。鹽酸石蒜堿（LH）對C8161細(xì)胞增殖的半數(shù)抑制濃度為0.99μM，能有效抑制C8161細(xì)胞主導(dǎo)的體內(nèi)腫瘤新生血管的形成和體外類血管網(wǎng)狀結(jié)構(gòu)的形成；作用機(jī)制研究揭示，LH可以下調(diào)血管形成關(guān)鍵基因VE-cadherin在C8161細(xì)胞的表達(dá)，化學(xué)發(fā)光實(shí)驗(yàn)顯示LH可明顯抑制VE-cadherin啟動(dòng)子的活性。另外，LH可有效抑制C8161細(xì)胞增殖，使細(xì)胞周期阻滯于G0/G1期，而對細(xì)胞凋亡的作用不大；其機(jī)理與誘導(dǎo)細(xì)胞周期抑制物p21的高表達(dá)密切相關(guān)。此外，我們還研究了另一種中草藥單體鹽酸藥根堿JH的抗黑色素瘤作用。JH對C8161細(xì)胞體外增殖的半數(shù)抑制濃度為47.35μM，，并能有效抑制C8161細(xì)胞主導(dǎo)的體內(nèi)腫瘤新生血管的形成和體外類血管網(wǎng)狀結(jié)構(gòu)的形成，其機(jī)理與抑制VE-cadherin在C8161細(xì)胞的表達(dá)有關(guān)；另外，JH可使C8161細(xì)胞周期阻滯于G0/G1期，而對C8161細(xì)胞凋亡無明顯影響，無明顯毒副作用。綜上所述，中草藥單體鹽酸石蒜堿和鹽酸藥根堿具有抗人高轉(zhuǎn)移黑色素瘤C8161細(xì)胞主導(dǎo)的腫瘤新生血管形成的作用，其機(jī)制很可能是通過抑制VE-cadherin基因的轉(zhuǎn)錄，降低C8161細(xì)胞中VE-cadherin的表達(dá)水平；兩者同時(shí)具有抑制C8161黑色素瘤生長和細(xì)胞增殖的作用。目前，國內(nèi)外尚無LH和JH抗腫瘤血管形成研究的報(bào)道，本研究將為未來中醫(yī)中藥抗新生血管和黑色素瘤有效藥物的研發(fā)提供新的信息和找到了新的突破口。
[Abstract]:Melanoma is a malignant tumor that seriously endangers human health. In recent years, the incidence and mortality of melanoma have increased rapidly. However, at present, the pathogenesis of malignant melanoma is not clear, and there is a lack of effective drugs, and the existing anti-melanoma Chinese herbal medicine is not effective, so it is necessary to explore new and more effective anti-cancer Chinese herbal medicine. Using tumor cells as a model, we selected two Chinese herbal medicines, Lycoris sativa and Coptis chinensis, which have a good anti-melanoma effect from more than 120 kinds of Chinese herbal medicines. The antiangiogenic effects of Lycorin (LH) and Rhizopine (JH) on melanoma were studied. It was found that both of them could inhibit the angiogenesis of human melanoma C8161 cells. The 50% inhibitory concentration of Lycorine (LH) on the proliferation of C8161 cells was 0.99 渭 m, which could effectively inhibit the formation of tumor angiogenesis and angioid reticular structure in vitro. The mechanism of LH could down-regulate the expression of angiogenesis key gene VE-cadherin in C8161 cells. Chemiluminescence assay showed that LH could significantly inhibit the activity of VE-cadherin promoter. In addition, LH could effectively inhibit the proliferation of C8161 cells and block the cell cycle in G0/G1 phase, but had little effect on cell apoptosis, and its mechanism was closely related to the overexpression of cell cycle inhibitor p21. In addition, We also studied the anti-melanoma effect of JH, another Chinese herbal monomer, and its inhibitory effect on the proliferation of C8161 cells in vitro. The median inhibitory concentration of JH on the proliferation of C8161 cells in vitro was 47.35 渭 m, and it could effectively inhibit the angiogenesis of tumor cells dominated by C8161 cells. The formation of vascular-like reticular structures in vitro, The mechanism is related to the inhibition of VE-cadherin expression in C8161 cells, in addition, JH can block the cell cycle in G0/G1 phase, but has no obvious effect on the apoptosis of C8161 cells. To sum up, Chinese herbal monomers Lycorine Hydrochloride and Rhizopine Hydrochloride have the effect of anti-tumor angiogenesis dominated by human high metastatic melanoma C8161 cells, and its mechanism is probably by inhibiting the transcription of VE-cadherin gene. Both of them can inhibit the growth and proliferation of C8161 melanoma. At present, there are no reports of LH and JH anti-tumor angiogenesis at home and abroad. This study will provide new information and find a new breakthrough for the research and development of anti-angiogenic and melanoma effective drugs of traditional Chinese medicine in the future.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R739.5
本文編號：2160330
[Abstract]:Melanoma is a malignant tumor that seriously endangers human health. In recent years, the incidence and mortality of melanoma have increased rapidly. However, at present, the pathogenesis of malignant melanoma is not clear, and there is a lack of effective drugs, and the existing anti-melanoma Chinese herbal medicine is not effective, so it is necessary to explore new and more effective anti-cancer Chinese herbal medicine. Using tumor cells as a model, we selected two Chinese herbal medicines, Lycoris sativa and Coptis chinensis, which have a good anti-melanoma effect from more than 120 kinds of Chinese herbal medicines. The antiangiogenic effects of Lycorin (LH) and Rhizopine (JH) on melanoma were studied. It was found that both of them could inhibit the angiogenesis of human melanoma C8161 cells. The 50% inhibitory concentration of Lycorine (LH) on the proliferation of C8161 cells was 0.99 渭 m, which could effectively inhibit the formation of tumor angiogenesis and angioid reticular structure in vitro. The mechanism of LH could down-regulate the expression of angiogenesis key gene VE-cadherin in C8161 cells. Chemiluminescence assay showed that LH could significantly inhibit the activity of VE-cadherin promoter. In addition, LH could effectively inhibit the proliferation of C8161 cells and block the cell cycle in G0/G1 phase, but had little effect on cell apoptosis, and its mechanism was closely related to the overexpression of cell cycle inhibitor p21. In addition, We also studied the anti-melanoma effect of JH, another Chinese herbal monomer, and its inhibitory effect on the proliferation of C8161 cells in vitro. The median inhibitory concentration of JH on the proliferation of C8161 cells in vitro was 47.35 渭 m, and it could effectively inhibit the angiogenesis of tumor cells dominated by C8161 cells. The formation of vascular-like reticular structures in vitro, The mechanism is related to the inhibition of VE-cadherin expression in C8161 cells, in addition, JH can block the cell cycle in G0/G1 phase, but has no obvious effect on the apoptosis of C8161 cells. To sum up, Chinese herbal monomers Lycorine Hydrochloride and Rhizopine Hydrochloride have the effect of anti-tumor angiogenesis dominated by human high metastatic melanoma C8161 cells, and its mechanism is probably by inhibiting the transcription of VE-cadherin gene. Both of them can inhibit the growth and proliferation of C8161 melanoma. At present, there are no reports of LH and JH anti-tumor angiogenesis at home and abroad. This study will provide new information and find a new breakthrough for the research and development of anti-angiogenic and melanoma effective drugs of traditional Chinese medicine in the future.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2012
【分類號】：R739.5
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
1 秦昆明;李笑;徐昭;蔡寶昌;;石蒜堿及其衍生物的藥理作用研究概況[J];北京聯(lián)合大學(xué)學(xué)報(bào)(自然科學(xué)版);2009年01期
2 代春美;王伽伯;孔維軍;肖小河;彭成;趙艷玲;金城;;微量熱法研究黃連及其主要組分配伍的抑菌作用[J];化學(xué)學(xué)報(bào);2010年10期
3 李明;王天曉;;中藥功勞木提取物對腫瘤MDR的逆轉(zhuǎn)作用[J];河南大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2007年02期
4 劉小珊;蔣紀(jì)愷;;石蒜堿對人白血病U937細(xì)胞的凋亡誘導(dǎo)及作用機(jī)制[J];山東醫(yī)藥;2008年02期
5 陳安家,蘇德釗,高繼才;藥根堿與血清白蛋白相互作用研究[J];山西醫(yī)科大學(xué)學(xué)報(bào);1999年S1期
6 劉法錦;孫冬梅;魯佳慧;胥愛麗;;薄層色譜掃描法測定黃連吳茱萸藥對中黃連生物堿的含量[J];中成藥;2010年01期
7 王天曉;李克;王世廣;叢悅;王穎瑩;;藥根堿誘導(dǎo)白血病K562細(xì)胞凋亡的研究[J];中國藥學(xué)雜志;2010年23期
8 楊清明,陳麗貞;細(xì)胞凋亡及其在腫瘤學(xué)的意義[J];中國腫瘤臨床與康復(fù);1997年01期
9 李佳川;孟憲麗;范昕建;賴先榮;張藝;曾勇;;黃連改善胰島素抵抗藥效物質(zhì)基礎(chǔ)研究[J];中國中藥雜志;2010年14期
10 郭青;吳丹;孫姍;;反相離子對高效液相色譜法測定益氣止血顆粒中3種生物堿成分[J];中藥新藥與臨床藥理;2009年01期
本文編號：2160330
本文鏈接：http://sikaile.net/yixuelunwen/pifb/2160330.html
最近更新
教材專著
