【摘要】：第一部分椿皮中二氯甲烷提取部位化學(xué)成分的研究臭椿(Ailanthus altissima Swingle)又名樗木,為苦木科(Simaroubaceae)臭椿屬落葉喬木,因葉上油腺破裂后有奇臭而得名,為中國(guó)本土樹種,在我國(guó)分布廣泛,除黑龍江、吉林和海南省外,全國(guó)各地均有分布。于18世紀(jì)作為觀賞植物傳入北美和歐洲,到目前為止,臭椿已經(jīng)在歐洲廣泛分布,同時(shí)分布在美國(guó)各地,現(xiàn)在已成為美國(guó)七個(gè)主要樹種之一。椿皮為臭椿的干燥樹皮或根皮,為我國(guó)民間常用中草藥,具有清熱、燥濕、止血、消炎、殺蟲等功效,可用于治療子宮出血、赤白帶下、久瀉久痢、濕熱瀉痢、便血及崩漏疾病。近年來(lái)研究表明,椿皮的提取物中因具有抗阿米巴原蟲活性,故可作為除蟲劑使用,同時(shí)經(jīng)研究證實(shí),它還具有明顯的抗癌作用,可用于治療結(jié)腸癌、宮頸癌、直腸癌等癌癥,還具有抗非洲淋巴細(xì)胞瘤病毒和抗結(jié)核菌的作用。椿皮主要化學(xué)成分有苦木苦味素、揮發(fā)性成分、萜類化合物、生物堿類等,其中最引人注目的化學(xué)成分就是苦木苦味素,而苦木苦味素類化合物多為四環(huán)二萜內(nèi)酯及五環(huán)二萜內(nèi)酯,是苦木科植物的特征性成分。臭椿屬是苦木苦味素類化學(xué)成分比較集中的屬級(jí)單位,而臭椿是臭椿屬中研究比較多的一種藥用植物,本研究對(duì)臭椿皮的化學(xué)成分中二氯甲烷提取部位進(jìn)行了研究。目的：以椿皮為研究對(duì)象,利用各種分離手段對(duì)其化學(xué)成分尤其是苦木苦味素類化學(xué)成分進(jìn)行系統(tǒng)研究,并采用波譜學(xué)及光譜學(xué)方法,包括：13C-NMR,1H-NMR, HMQC,COSY, HMBC, NOESY等方法對(duì)分離得到的單體化合物進(jìn)行平面結(jié)構(gòu)和立體結(jié)構(gòu)的鑒定,為發(fā)現(xiàn)新的藥物先導(dǎo)性化合物奠定基礎(chǔ)。方法：取干燥的椿皮50 Kg,以95%乙醇熱回流提取,濃縮后得到總提物。將總提物分散在飽和氯化鈉溶液中,分別以石油醚、二氯甲烷、乙酸乙酯和正丁醇萃取,分別濃縮,得到各提取部位,其中二氯甲烷萃取部位260 g。采用硅膠層析、葡聚糖凝膠、制備薄層和制備高效液相色譜法對(duì)上述二氯甲烷萃取部位的化學(xué)成分進(jìn)行分離,得到的單體化合物采用現(xiàn)代化的分析方法如13C-NMR,'H-NMR, HMQC, COSY, HMBC和NOESY鑒定其化學(xué)結(jié)果。結(jié)果：從椿皮中分離并鑒定了9個(gè)化合物,鑒定結(jié)果如下：vanillin (1), stigmast-4-en-3-one (2), isoailanthone (3), shinjudilactone (4), ailanthone (5), shinjulactone B (6),6a-tigloyloxychaparrin(7),2-dihydroailanthone (8), 12-dihydroisoailanthone (9).第二部分椿皮中二氯甲烷提取部位及化合物抗腫瘤活性的研究椿皮始載于我國(guó)第一部藥典《唐本草》中,為我國(guó)傳統(tǒng)中藥材,古時(shí)所用椿皮系指香椿和臭椿的干皮或根皮,其中以臭椿皮為好。我國(guó)歷代都有對(duì)椿皮藥用的記載：《食療本草》載其有治痢疾、殺蛔蟲之效；《活性論》中記載臭椿皮能治療赤白痢、腸滑、痔疾瀉血不止；《婦人良方》中記載用,以臭椿根與漢椒焙燒,加連根蔥同煎后熏洗,可治療婦女產(chǎn)后腸脫不收,與蜂蜜水煎服可治療痔瘡,單用椿皮的水煎液可治療瘡癬等�，F(xiàn)代藥理學(xué)研究發(fā)現(xiàn),椿皮除了具有上述傳統(tǒng)功效外,還兼有抗腫瘤、抗結(jié)核菌、抗EB病毒、抗阿米巴、抗瘧等作用,尤以抗腫瘤作用明顯,其所含的化學(xué)成分苦木苦味素有治療結(jié)腸癌、宮頸癌、直腸癌等作用,是目前藥理學(xué)研究的熱點(diǎn)之一。本研究將椿皮的抗腫瘤活性研究作為分離、純化和精制椿皮中各個(gè)化合物的重要依據(jù),以“重在應(yīng)用,面向開(kāi)發(fā)”為本研究的指導(dǎo)原則。目的：以臭椿皮為研究對(duì)象,利用現(xiàn)代化的腫瘤細(xì)胞活性篩選技術(shù)手段,對(duì)椿皮中的各個(gè)提取部位以及各分離、純化和制備的化合物進(jìn)行系統(tǒng)的抗腫瘤活性篩選,以各個(gè)組分的腫瘤細(xì)胞增值抑制率為指標(biāo)進(jìn)行活性分析。分別以ailanthone和2-dihydroailanthone為代表化合物進(jìn)行抗腫瘤作用機(jī)制的研究。方法：1以MTT法檢測(cè)不同提取部位及化合物的抗腫瘤活性。試驗(yàn)設(shè)空白對(duì)照組、DMSO溶劑對(duì)照組及待測(cè)藥物組(提取部位的濃度分別為1μg/mL,10 μg/mL和100 μg/mL;化合物的濃度分別為0.01 μg/mL,0.1μg/mL,1 μg/mL,10 μg/mL和100μg/mL)。2 Ailanthone和2-dihydroailanthone對(duì)MCF-7人乳腺癌細(xì)胞和U251人神經(jīng)膠質(zhì)瘤細(xì)胞抗腫瘤作用機(jī)制的研究。以濃度不同濃度的ailanthone和2-dihydroailanthone分別對(duì)兩種腫瘤細(xì)胞進(jìn)行增殖抑制率檢測(cè)、細(xì)胞凋亡檢測(cè)、細(xì)胞周期檢測(cè)以及RT-PCR檢測(cè)Bax和Bcl-2 mRNAd的表達(dá)和Western blot法檢測(cè)Bax及Bcl-2蛋白表達(dá)的研究。結(jié)果：1測(cè)定了不同提取部位及化合物抗腫瘤活性的篩選,實(shí)驗(yàn)結(jié)果顯示,對(duì)于13個(gè)腫瘤細(xì)胞株而言,不用的提取部位及化合物具有不同的抗腫瘤活性,而化合物2和4在高、中、低三個(gè)濃度的抗腫瘤活性均比較低。對(duì)化合物1、3、5、和6的IC50值進(jìn)行了測(cè)定。實(shí)驗(yàn)結(jié)果顯示,以上4個(gè)化合物對(duì)不同的腫瘤細(xì)胞的IC50值是不相同的,在13種腫瘤細(xì)胞上進(jìn)行的IC50值測(cè)定數(shù)據(jù)顯示,化合物5、6對(duì)13個(gè)腫瘤細(xì)胞的IC50值小于陽(yáng)性藥順鉑(cisplatin),表明它們對(duì)13個(gè)腫瘤細(xì)胞的抑制作用優(yōu)于陽(yáng)性對(duì)照藥順鉑；化合物3對(duì)U251、Hela、AsPC-1、HCT116、AGS、SMMC-7721、 U-2OS、CCRF-CEM細(xì)胞的IC50值均小于陽(yáng)性對(duì)照藥順鉑,表明化合物3對(duì)這9個(gè)腫瘤細(xì)胞的抑制作用優(yōu)于陽(yáng)性對(duì)照藥順鉑。化合物1對(duì)U251、Hela、HCT116、AGS、SMMC-7721、U-2OS、CCRF-CEM細(xì)胞的IC50值均小于陽(yáng)性對(duì)照藥順鉑,表明化合物1對(duì)這7個(gè)腫瘤細(xì)胞的抑制作用優(yōu)于陽(yáng)性藥順鉑。結(jié)果評(píng)定：合成化合物或植物提取純品的IC5010 μg/mL或植物提取物的IC5020 μg/mL時(shí),則判斷樣品在體外對(duì)腫瘤細(xì)胞有殺滅作用。2不同濃度的ailanthone作用MCF-7人乳腺癌細(xì)胞24 h、48 h以及72 h后,MCF-7人乳腺癌細(xì)胞的存活率分別逐漸降低,表明ailanthone對(duì)人乳腺癌MCF-7細(xì)胞的生長(zhǎng)有明顯的抑制作用,而且呈現(xiàn)時(shí)間和濃度的雙重依賴性。而不同濃度的2-dihydroailanthone對(duì)U251人神經(jīng)膠質(zhì)瘤細(xì)胞的抑制作用也同樣很明顯。流式細(xì)胞儀檢測(cè)不同濃度的ailanthone和2-dihydroailanthone分別作用于MCF-7人乳腺癌細(xì)胞和U251入神經(jīng)膠質(zhì)瘤細(xì)胞48 h后的凋亡實(shí)驗(yàn)結(jié)果表明,凋亡率明顯高于空白對(duì)照組,且隨藥物濃度增高細(xì)胞凋亡率明顯增高,差異有統(tǒng)計(jì)學(xué)意義(P0.05)。而不同濃度的藥物作用于腫瘤細(xì)胞48h后的細(xì)胞周期實(shí)驗(yàn)結(jié)果表明,G0/G1期的細(xì)胞百分比逐漸增加,而S期和G2/M期的細(xì)胞百分比逐漸降低,表明細(xì)胞阻滯發(fā)生在G0/G1期。通過(guò)RT-PCR檢測(cè)發(fā)現(xiàn),不同濃度的ailanthone和2-dihydroailanthone分別作用于人乳腺癌MCF-7細(xì)胞和U251人神經(jīng)膠質(zhì)瘤細(xì)胞48 h后,Bax/gapdh的百分比逐漸升高,而Bcl-2/gapdh的百分比逐漸降低,實(shí)驗(yàn)結(jié)果表明,Bax mRNA的表達(dá)隨藥物濃度的增加而上升,Bcl-2 mRNA的表達(dá)隨藥物濃度的增加而降低,呈現(xiàn)一定的劑量依賴性,說(shuō)明這兩種藥物能增加Bax mRNA的表達(dá),并抑制Bcl-2 mRNA的表達(dá),且具有一定的量效關(guān)系。Western blot法檢測(cè)Bax及Bcl-2蛋白表達(dá)結(jié)果。不同濃度的ailanth one和-dihydroailanthone分別作用人乳腺癌MCF-7和U251人神經(jīng)膠質(zhì)瘤細(xì)胞48 h后,檢測(cè)Bax. Bcl-2蛋白表達(dá),bax/β-actin的百分比逐漸升高,而bcl-2/β-actin百分比則逐漸降低,實(shí)驗(yàn)結(jié)果表明,與對(duì)照組比較,不同劑量的藥物可使Bcl-2表達(dá)降低,而Bax表達(dá)增加,且呈現(xiàn)一定的劑量依賴性關(guān)系。第三部分椿皮中二氯甲烷提取部位分散片制備工藝與質(zhì)量標(biāo)準(zhǔn)的研究分散片具有穩(wěn)定性好、便于攜帶、服用方便、崩解和溶出速度快、生物利用度較高等優(yōu)點(diǎn),可直接口服或投入水中分散后服用,尤其適于吞服困難的患者,并且口感良好,提高了患者的依從性,日益受到廣大患者的青睞。目的：以椿皮中二氯甲烷提取部位所提取、分離的有效部位為研究對(duì)象,利用現(xiàn)代化的中藥藥劑學(xué)技術(shù)手段和方法,使其具有現(xiàn)代劑型的各種特征,對(duì)其進(jìn)行藥劑學(xué)研究。在具體的研究中制備快速釋放和穩(wěn)定性好的臭椿苦酮提取物分散片,著重研究制備過(guò)程中的影響因素和最優(yōu)工藝,并對(duì)分散片進(jìn)行質(zhì)量評(píng)價(jià)。此研究的意義在于通過(guò)藥劑學(xué)研究,將難溶于水溶液的臭椿苦酮提取物,制備成為分散片,從而為椿皮在臨床中的廣泛應(yīng)用打下基礎(chǔ)。方法：采用紫外分光光譜法建立臭椿苦酮提取物體外分析方法,以測(cè)定其含量,為臭椿苦酮提取物分散片的處方篩選、工藝研究、質(zhì)量研究及體外分析奠定基礎(chǔ)。利用單因素考查和正交設(shè)計(jì)法,以12小時(shí)累計(jì)溶出度為指標(biāo),對(duì)臭椿苦酮提取物分散片的處方進(jìn)行研究,篩選最佳制備方法。結(jié)果：根據(jù)處方工藝研究結(jié)果,擬定了臭椿苦酮提取物分散片的處方,進(jìn)行了分散片的小試制備,片劑各檢查項(xiàng)以及脆碎度、分散均勻性和含量均滿足質(zhì)量標(biāo)準(zhǔn)要求。參考中國(guó)藥典2010版中有關(guān)分散片的相關(guān)規(guī)定,制定了本品的質(zhì)量標(biāo)準(zhǔn),并對(duì)含量測(cè)定和體外溶出度進(jìn)行了方法學(xué)研究。以紫外分光光度法測(cè)定含量。方法學(xué)研究結(jié)果表明,臭椿苦酮在1.5μg/mL-30 μg/mL的濃度范圍內(nèi),其吸收度與濃度呈良好的線性關(guān)系,相關(guān)系數(shù)為0.9997。重現(xiàn)性及穩(wěn)定性良好,精密度實(shí)驗(yàn)RSD為0.15%,符合精密度要求,回收率值為99.02%。結(jié)論：1本研究對(duì)椿皮(Ailanthus altissima bark)的化學(xué)成分中二氯甲烷部位進(jìn)行了系統(tǒng)的研究,分離并鑒定了9個(gè)化合物。結(jié)合本研究所得到的化合物的波譜數(shù)據(jù)及查閱文獻(xiàn),總結(jié)了不同取代基的苦木素類化合物的核磁共振波譜特征,為此類化合物的快速結(jié)構(gòu)鑒定提供了依據(jù)。2本研究對(duì)椿皮的化學(xué)成分中二氯甲烷部位中的各個(gè)有效部位和單體化合物進(jìn)行了抗腫瘤作用研究,發(fā)現(xiàn)各個(gè)有效部位和單體化合物基本上都有一定的抗腫瘤活性,甚至有的化合物的活性超過(guò)了陽(yáng)性對(duì)照藥(順鉑)。以ailanthone和2-dihydroailanthone為代表化合物,通過(guò)腫瘤細(xì)胞凋亡檢測(cè)、腫瘤細(xì)胞周期檢測(cè)、RT-PCR和蛋白印跡等實(shí)驗(yàn)方法研究了ailanthone和2-dihydroailanthone對(duì)MCF-7人乳腺癌細(xì)胞和U251人神經(jīng)膠質(zhì)細(xì)胞的抗腫瘤作用機(jī)制,實(shí)驗(yàn)結(jié)果發(fā)現(xiàn),這兩種藥物所表現(xiàn)的抗腫瘤作用與下調(diào)Bcl-2的基因表達(dá),同時(shí)上調(diào)Bax基因表達(dá)有關(guān)。為有針對(duì)性的分離、純化化合物以及進(jìn)行下一步的藥劑學(xué)研究提供了指導(dǎo)原則。3以臭椿苦酮提取物為原料,按照中國(guó)藥典對(duì)分散片的有關(guān)規(guī)定,進(jìn)行處方組成與制備工藝的研究,完成了分散片的制備工藝,建立了臭椿苦酮提取物分散片的質(zhì)量評(píng)價(jià)方法,并進(jìn)行了方法學(xué)和穩(wěn)定性研究,各項(xiàng)指標(biāo)均達(dá)到中國(guó)藥典2010版對(duì)分散片的要求。
[Abstract]:The first part is about the chemical constituents of dichloromethane extracted from the bark of Chinese toon. Ailanthus altissima Swingle is a deciduous tree of the genus Ailanthus. It is named for its peculiar odor after the rupture of the epifoliar oil gland. It is a native tree species in China and widely distributed in China except Heilongjiang, Jilin and Hainan provinces. As an ornamental plant, Ailanthus altissima was introduced into North America and Europe in the 18th century. Up to now, it has been widely distributed in Europe, and is now one of the seven major tree species in the United States. Recent studies have shown that the extract of Chinese toon bark can be used as an insecticide because of its anti-amoeba activity. At the same time, it has been proved that it has obvious anti-cancer effect and can be used in the treatment of colon cancer, cervical cancer and rectum cancer. The main chemical constituents of Chinese toon bark are bitter wood picrin, volatile constituents, terpenoids, alkaloids, etc. The most striking chemical constituents are bitter wood picrin, and bitter wood picrins are mostly tetracyclic diterpenoid lactones and pentacyclic diterpenoids. Aim: To study the extracting parts of dichloromethane from the bark of Ailanthus altissima. The chemical constituents, especially bitter lignans, were systematically studied by various methods, including 13C-NMR, 1H-NMR, HMQC, COSY, HMBC and NOESY. The planar and stereoscopic structures of the isolated monomers were identified by spectroscopic and spectroscopic methods, including 13C-NMR, 1H-NMR, HMQC, COSY, HMBC and NOESY. METHODS: The dried Chinese toon bark was extracted by heat reflux with 95% ethanol and concentrated to obtain the total extract. Dextran gel, preparation of thin layer chromatography and preparation of high performance liquid chromatography were used to separate the chemical constituents of the above dichloromethane extracts. The monomers were identified by modern analytical methods such as 13C-NMR,'H-NMR, HMQC, COSY, HMBC and NOESY. The results were as follows: vanillin (1), stigmast-4-en-3-one (2), isoailanthone (3), shinjudilactone (4), ailanthone (5), shinjulactone B (6), 6a-tigloyloxy chaparrin (7), 2-dihydroailanthone (8), 12-dihydroisoanthone (9). Part II The extraction site of dichloromethane from Chinese toon bark and the antitumor activity of the compounds were studied. In the first Chinese Pharmacopoeia , it is a traditional Chinese medicinal material. The bark of Ailanthus altissima used in ancient times refers to the dry skin or root bark of Chinese toon and Ailanthus altissima, especially the bark of Ailanthus altissima. Slip, hemorrhoids and diarrhea of blood more than recorded in the use of the root of Ailanthus altissima and Chinese pepper roast, plus the root of onion with the decoction after fumigation, can treat postpartum intestinal detachment of women, with honey decoction can treat hemorrhoids, single use of the decoction of the skin of Chinese toon can treat sores and tinea, etc. Modern pharmacological research found that in addition to the above-mentioned traditional efficacy, but also have anti-tuberculosis. Tumor, anti-tuberculosis bacteria, anti-EB virus, anti-amoeba, anti-malaria and other effects, especially anti-tumor effect is obvious, its chemical constituents bitter wood picrin has the effect of treating colon cancer, cervical cancer, rectal cancer, and so on, is currently one of the hot spots of pharmacological research. Objective: To screen the antitumor activity of the extracts and the compounds separated, purified and prepared from the bark of Ailanthus altissima by modern screening techniques of tumor cell activity. Inhibitory rate of tumor cell proliferation of each component was analyzed. The antitumor mechanism was studied by using ailanthone and 2-dihydroailanthone as representative compounds. Methods: 1 The antitumor activity of different extracts and compounds was detected by MTT method. The antitumor mechanisms of 2-dihydroailanthone and 2-Ailanthone on MCF-7 human breast cancer cells and U251 human glioma cells at different concentrations were studied. One and 2-dihydroailanthone were used to detect the inhibitory rate of proliferation, apoptosis, cell cycle, Bax and Bcl-2 mRNAd expression by RT-PCR and Bax and Bcl-2 protein expression by Western blot respectively. The results showed that for 13 tumor cell lines, the unused extracts and compounds had different antitumor activities, while compounds 2 and 4 had relatively low antitumor activities at high, medium and low concentrations. The IC50 values of compounds 5 and 6 on 13 tumor cells were lower than those of the positive drug cisplatin, suggesting that their inhibitory effect on 13 tumor cells was better than that of the positive control drug cisplatin; compound 3 on U251, Hela, AsPC-1, HCT116, AGS, SMMC-7721, U-2OS, CCRF-CEM The IC50 values of the cells were lower than those of the positive control drug cisplatin, indicating that the inhibitory effect of compound 3 on the 9 tumor cells was better than that of the positive control drug cisplatin. The IC50 values of compound 1 on U251, Hela, HCT116, AGS, SMMC-7721, U-2OS, CCRF-CEM cells were lower than those of the positive control drug cisplatin, indicating that compound 1 had better inhibitory effect on the 7 tumor cells than that of the positive control drug cisplatin. Results: When the IC5010 ug/mL of synthetic compound or plant extract or IC5020 ug/mL of plant extract were used, it was judged that the sample could kill tumor cells in vitro. 2 Different concentrations of ailanthone could reduce the survival rate of MCF-7 breast cancer cells 24 h, 48 h and 72 h after treatment, respectively. The results showed that the growth of human breast cancer MCF-7 cells was significantly inhibited by ailanthone in a time-and concentration-dependent manner. The inhibitory effect of 2-dihydroailanthone on U251 glioma cells was also evident. Different concentrations of ailanthone and 2-dihydroailanthone were detected by flow cytometry. The results showed that the apoptosis rate of MCF-7 breast cancer cells and U251 glioma cells 48 hours after they were treated with MCF-7 and U251 respectively was significantly higher than that of the blank control group. The apoptosis rate of MCF-7 breast cancer cells and U251 glioma cells was significantly higher than that of the blank control group (P 0.05). The results showed that the percentage of cells in G0/G1 phase increased gradually, while that in S phase and G2/M phase decreased gradually, indicating that cell block occurred in G0/G1 phase. The results showed that the expression of Bax mRNA increased with the increase of drug concentration, and the expression of Bcl-2 mRNA decreased with the increase of drug concentration. The expression of Bcl-2 mRNA showed a dose-dependent manner, indicating that the two drugs could increase the expression of Bax mRNA and inhibit the expression of Bcl-2 mRNA. Western blot was used to detect the expression of Bax and Bcl-2 protein. After 48 hours of treatment with different concentrations of ailanth one and dihydroailanthone respectively, the expression of Bax.Bcl-2 protein was detected in human breast cancer MCF-7 and U251 glioma cells. The percentage of bax/beta-actin increased gradually, while the percentage of bcl-2/beta-actin decreased gradually. The results showed that the expression of Bcl-2 was decreased and the expression of Bax was increased in a dose-dependent manner when compared with the control group. Part III Study on preparation technology and quality standard of dichloromethane extract dispersible tablets from Chinese toon bark It has the advantages of high speed, high bioavailability and so on. It can be taken orally or dispersed in water directly. It is especially suitable for patients with dysphagia. It has a good taste and improves the compliance of patients. It is increasingly favored by the majority of patients. Pharmaceutical studies on the dispersible tablets of Toona bitter ketone extract with rapid release and good stability were carried out. The influencing factors and optimum technology in the preparation process were emphatically studied, and the quality of dispersible tablets was evaluated. The significance of this study is to prepare a dispersible tablet from the extract of Ailanthus altissima which is difficult to dissolve in aqueous solution by pharmaceutics research, so as to lay a foundation for its wide application in clinic. Methods: A method for in vitro analysis of the extract of Ailanthus altissima was established by ultraviolet spectroscopy to determine the content of the extract. The formulation, technology, quality and in vitro analysis of the dispersible tablets were studied by single factor test and orthogonal design. The 12-hour cumulative dissolution was used as the index to select the best preparation method. The formulation of the dispersible tablets was prepared in a small scale. The tablets were tested and the fragility, uniformity and content of the dispersible tablets met the requirements of the quality standards. The results showed that the absorbance of Toona bitter ketone was linear with the concentration in the range of 1.5 ug/mL-30 ug/mL. The correlation coefficient was 0.9997. The RSD of precision test was 0.15%, which met the precision requirement and the recovery rate was 99.02%. Nine compounds were isolated and identified from the chemical constituents of Ailanthus altissima bark. The NMR spectroscopic characteristics of different substituents of bitter lignin compounds were summarized based on the spectroscopic data and references. In this study, we studied the anti-tumor effects of various active parts and monomers of dichloromethane in the chemical constituents of Chinese toon bark. It was found that the active parts and monomers of Chinese toon bark basically had certain anti-tumor activities, and even some of them were more active than the positive control drug (cisplatin). (2) Using ailanthone and 2-dihydroailanthone as representative compounds, we detected apoptosis, cell cycle, RT-PCR and protein of tumor cells.
【學(xué)位授予單位】：河北醫(yī)科大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2016
【分類號(hào)】：R96

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