槲皮素抗肿瘤作用的研究

槲皮素是一种具有多种生物活性的黄酮类化合物.本文从抑制肿瘤细胞增殖,逆转肿瘤细胞多药耐药和与其他药物联用增强抗肿瘤作用等几方面,对槲皮素的抗瘤作用一综述.     

基于网络药理学探讨毛兰素抗肿瘤作用机制研究

目的 基于网络药理学探讨毛兰素抗肿瘤的作用机制。方法 利用HT Docking数据库对毛兰素潜在靶点进行预测,运用Cytoscape软件和GeneMANIA网站对毛兰素潜在靶点进行分析。结果 共得到101种人源潜在靶蛋白。有13条通路与肿瘤相关,包括肿瘤通路、胶质瘤通路、前列腺癌通路、膀胱癌通路、胃癌通路、结直肠癌通路、胰腺癌通路、非小细胞肺癌通路、子宫内膜癌通路、癌症蛋白聚糖通路、癌症中心碳代谢通路、癌症胆碱代谢通路及急性髓性白血病通路。蛋白之间相互作用主要通过基因相关性、共享蛋白域、物理相关性、共定位、预测、蛋白共表达及通路表现出来。蛋白质相互作用网络分析显示,基因相关性占30.45%、预测占26.99%、共享蛋白域占15.69%、物理相关性占11.58%、共定位占5.99%、蛋白共表达占5.14%、通路占4.15%。结论 毛兰素通过AKT1、CDK6、AR、BRAF、CSF1R、DAPK1等靶点发挥抗肿瘤效应,这些靶点参与13条肿瘤相关通路,可为后续抗肿瘤实验研究提供理论参考和指导方向。     

二氢槲皮素与二氢杨梅素的抗肿瘤活性对比

目的:研究二氢槲皮素和二氢杨梅素对H22 荷瘤小鼠抑瘤作用。方法:建立小鼠H22 移植性肿瘤模型(除空白外)。造模24 h 后分成6 组:模型组,阳性对照组(环磷酰胺25 mg/ kg),二氢槲皮素和二氢杨梅素高、低剂量组(30、10 mg/kg),除阳性对照组腹腔给药,其余各组均灌胃给药,测定其对H22 荷瘤小鼠抑瘤率、免疫器官指数、生化指标和细胞因子含量的影响,并通过HE 染色,观察瘤组织内坏死程度。结果:二氢槲皮素和二氢杨梅素高、低剂量组(30 mg/ kg、10 mg/ kg)均对肿瘤具有一定抑制作用,且均可提高H22 荷瘤小鼠胸腺指数和脾指数,其中二氢槲皮素高剂量组(30 mg/ kg)抑瘤效果最佳,其抑瘤率为58.8%。二氢槲皮素和二氢杨梅素高、低剂量组均可升高H22 荷瘤小鼠细胞因子白细胞介素鄄2(IL-2)和肿瘤坏死因子 (TNF)的水平,升高超氧化物歧化酶(SOD)的水平,降低丙二醛(MDA)水平。此外,二氢槲皮素和二氢杨梅素高、低剂量组对H22 荷瘤小鼠肝肾功能没有毒理作用。结论:二氢槲皮素和二氢杨梅素高、低剂量组均对肿瘤具有一定抑制作用,其中二氢槲皮素组的作用较明显,且呈剂量依赖性,其作用机制可能与增强抗氧化能力、提高机体免疫功能和升高细胞因子水平有关。     

槲皮素对U937细胞系抑制增殖和诱导凋亡作用的研究

目的 探讨黄酮类化合物槲皮素（Que）对人类单核细胞白血病U937细胞系的抑制增殖和诱导凋亡的作用。方法 应用MTT法检测不同浓度槲皮素对U937细胞的增殖抑制作用；AO／PI荧光染色后倒置荧光显微镜下观察细胞形态学变化；琼脂糖凝胶电泳测定细胞DNA的片段化；应用流式细胞仪检测细胞凋亡率及细胞周期分布。结果槲皮素能明显抑制U937细胞增殖，并存在剂量-效应关系和时间-效应关系；诱导U937细胞出现凋亡所具有的形态学和生化特征；随着槲皮素浓度升高，凋亡细胞和坏死细胞比例增加；将细胞特异性地阻滞在S期，出现凋亡峰。结论 槲皮素能抑制U937细胞增殖，诱导细胞凋亡，并具有细胞周期特异性。     

槲皮素诱导人宫颈癌Hela细胞凋亡的作用

目的:检测槲皮素体外对人宫颈癌Hela细胞的增殖抑制及凋亡诱导作用,并探讨线粒体在诱导凋亡机制中的作用.方法:采用酸性磷酸酶法检测细胞增殖抑制率;丫啶橙(AO)/溴化乙锭(EB)荧光染色观测细胞形态结构变化;流式细胞仪检测线粒体膜电位（△ψm）.结果:槲皮素对人宫颈癌Hela细胞有明显的增殖抑制作用,且呈浓度和时间依赖性.经槲皮素作用48 h后,AO/EB染色可见细胞呈凋亡形态学改变.100 μmol/L槲皮素作用Hela细胞24、48 h后,与对照组相比线粒体膜电位下降.结论:槲皮素体外能抑制人宫颈癌Hela细胞生长,引起线粒体膜电位下降,诱导细胞凋亡.     

灵芝的抗肿瘤作用机制

70 年以来国内外一系列研究证明灵芝[ Ganodermalucidum(Leyss.ex Fr.)Karst.] 对动物移植性肿瘤具有抑制作用,可使瘤重减轻,生存时间延长。并认为灵芝多糖可能是灵芝抗肿瘤作用的重要有效成份[1]。然而,灵芝的抗肿瘤作用是如何产生的？灵芝是直接杀死肿瘤细胞,还是像一些学者推测的那样：灵芝是通过机体内部的抗肿瘤机制间接杀死肿瘤细胞,这些均是目前学术界关注的焦点。为此,我们采用体内外抗肿瘤实验方法和细胞分子生物学技术以及血清药理学方法探讨了灵芝的抗肿瘤作用及其机制。1 灵芝的体内抗肿瘤作用给Blab/c 小鼠皮下接种肉…     

槲皮素对U937细胞系抑制增殖和诱导凋亡作用的研究

目的探讨黄酮类化合物槲皮素(Que)对人类单核细胞白血病U937细胞系的抑制增殖和诱导凋亡的作用.方法应用MTT法检测不同浓度槲皮素对U937细胞的增殖抑制作用;AO/PI荧光染色后倒置荧光显微镜下观察细胞形态学变化;琼脂糖凝胶电泳测定细胞DNA的片段化;应用流式细胞仪检测细胞凋亡率及细胞周期分布.结果槲皮素能明显抑制U937细胞增殖,并存在剂量-效应关系和时间-效应关系;诱导U937细胞出现凋亡所具有的形态学和生化特征;随着槲皮素浓度升高,凋亡细胞和坏死细胞比例增加;将细胞特异性地阻滞在S期,出现凋亡峰.结论槲皮素能抑制U937细胞增殖,诱导细胞凋亡,并具有细胞周期特异性.     

鸡血藤活性成分及抗肿瘤作用研究

鸡血藤含化学成分复杂,具有抗肿瘤活性成分,显现出良好的抗病毒、抗肿瘤作用,对抗肿瘤研究具有重要意义。本文就鸡血藤活性成分提取工艺及其抗宫颈癌、乳腺癌、肝癌、肺癌的药理作用和肿瘤细胞的相关死亡通道进行系统综述,以掌握鸡血藤活性成分提取工艺技术及抗肿瘤药理学研究进展,以此为鸡血藤药用资源的开发利用及为后续的抗肿瘤研究提供理论依据。     

槲皮素对氧化高密度脂蛋白致内皮细胞损伤的保护作用

目的:研究槲皮素(Que)对含氧化高密度脂蛋白(oxHDL)血浆致人内皮细胞株(ECV304)损伤的保护作用。方法:常规培养ECV304细胞被分成5组:对照组(ECV304+HDL)、oxHDL组(ECV304+ox-HDL)、Que大剂量处理组(ECV304+oxHDL+80μmol/LQue)、Que中剂量处理组(ECV304+oxHDL+60μmol/LQue)及Que小剂量处理组(ECV304+oxHDL+40μmol/LQue),培养24h后平行检测各组ECV304形态、细胞内脂质过氧化物丙二醛(MDA)含量、细胞乳酸脱氢酶(LDH)活性。结果:中、大剂量组ECV304形态较oxHDL组有明显改善,更接近于对照组;与oxHDL组相比,中、大剂量Que处理组ECV304培养液中LDH活性及MDA含量明显降低(P<0.01),而小剂量Que处理组结果无显著差异(P>0.05)。结论:Que对oxHDL致ECV304损伤有保护作用。     

槲皮素对柔红霉素所致心肌损伤的保护作用

目的观察槲皮素(QUE)对柔红霉素(DNR)所致小鼠心肌损伤的保护作用．方法52只小鼠分5个实验组，1组作为空白对照组．1组用DNR诱导小鼠心肌损伤；1组用QUE灌胃给药后再用DNR诱导心肌损伤作为保护组；1组只给QUEE灌胃作为保护对照组；1组给予DMSO灌胃作为溶剂对照组．观察各组小鼠的血清心肌酶谱、心肌和血清中脂质过氧化产物丙二醛(MDA)的含量及超氧化物歧化酶(SOD)活性的变化．观察心脏大体改变．并制备病理切片，HE染色后，光镜下观察心肌形态学变化．结果DNR组小鼠的血清心肌酶谱显著升高．血清和心肌中MDA含量显著增高，SOD活性降低，引起心脏充血、水肿．心肌颗粒变性．灶性出血、坏死．而QUE保护组的心肌酶升高程度明显降低、血清和心肌组织中MDA含量无明显增加，SOD活性不降低，心肌无明显出血灶及颗粒变性．结论槲皮素对柔红霉素诱导的小鼠心肌损伤有保护作用．其机理可能与清除氧自由基、抗脂质过氧化损伤有关．     

Antitumour effect of Lactobacillus casei CRL 431 on different experimental tumours

We analysed the mechanisms of tumour inhibition by Lactobacillus casei CRL 431 orally administered, for fibrosarcome (non intestinal tumour, NIT) and for carcinoma (intestinal tumour, IT), both induced chemically. Balb/c mice were fed with L. casei (1.2×10⁹cel/day/mouse) for two consecutive days previous to the induction of the respective tumours. After IT induction, oral administration of L. casei was repeated cyclically every 5 days for 5 months. In order to determine the percentage of tumour inhibition in the NIT mice, morphometric studies were performed and TNFα levels in serum and spleen cells were determined. In the IT, macroscopic and histopathological studies were performed and the number of intestinal IgA⁺ and TNFα⁺ cells was determined. We demonstrated that L. casei CRL 431 inhibited the growth of both tumours. In the case of NIT animals treated with L. casei, the high levels of serum TNFα would play an important role in the inhibition of tumour growth due to its cytolytic activity against tumour cells. In the IT, the increase in IgA⁺ and TNFα⁺ cells could be involved in the inhibitory effect observed. Our results showed that the selection of the probiotic bacteria with antitumour activity would not be limited to the determination of the cytokines relevant to this activity because of the multifactorial etiology of the different cancers.     

Monitoring Antitumour Immune Response During Immunotherapy of Cancer

Cancer remains one of the most important public health concerns facing us today. Despite recent therapeutic developments, conventional therapies have provided only limited success in the management of patients with advanced disease. The recent discovery of tumour-associated antigens has led to a strong interest in immunotherapy as an alternative or adjuvant cancer treatment modality. Despite the expanding volumes of literature on this form of therapy confirming its strong anti-neoplastic effects in animals, much still remains to be elucidated with respect to its clinical applicability and effectiveness in human subjects. Clinical trials evaluating a wide variety of immunotherapeutic approaches in cancer patients are currently underway throughout the world and many have yielded promising preliminary results. In order to reach a better understanding of this potentially powerful therapeutic tool in a timely fashion, a methodical, multi-institutional approach is indispensable. All patients undergoing treatment should be monitored closely in order to correlate specific therapy-induced anti-tumour responses with clinical outcomes. This article provides a brief overview of specific assays currently used to monitor immune responses in these patients. Special emphasis is placed on the theory behind these tests and specific examples from the literature are provided.     

Induction of Systemic Antitumour Resistance with Targeted Polymers

Conjugates based on N- (2-hydroxypropyl)methacrylamide (HPMA) represent a new generation of antibody-targeted polymeric anticancer drugs with both cytotoxic and immunoprotecting/immunomobilizing activity. 20–90% of mice that are cured of EL4 mouse T-cell lymphoma, BCL1 mouse B-cell leukaemia and 38C13 mouse B-cell lymphoma by injection of doxorubicin-HPMA conjugate develop a long-lasting memory and systemic antitumour resistance. It is suggested that the main activity of the polymeric drug, directly after application is – due to the high level of the drug – of cytotoxic and cytostatic nature. Thereafter, long-term conjugates persist at low concentration in the circulation, which are capable of mobilizing the defence mechanisms of the host. Until now, seven patients with generalized carcinoma were treated with doxorubicin-HPMA–human-Ig conjugate. Disease stabilization, lasting from 6 to more than 18 months, was recorded.     

Antitumour effect of RA 233 alone and combined with radiotherapy

The effect of RA233 alone or in combination with radiation was investigated in vivo on the S180 sarcoma, the B16 melanoma and the Lewis lung carcinoma. The combined treatment was a significant improvement over radiation alone for the B16 and S180 tumours. RA233 alone did not influence the growth of these tumours. When the primary 3LL was irradiated, tumour size was unaffected but the number of pulmonary metastases was reduced. They were further reduced by the combination of RA233 and radiation. The number, volume and cytokinetics of the B16 cells and the 3LL cells were affected to varying degrees by RA233. The significance of these changes relative to the effects of RA233 are discussed.     

Advances in the Study of Antitumour Immunotherapy for Newcastle Disease Virus

This article reviews the preclinical research, clinical application and development of Newcastle disease virus (NDV) in the field of cancer therapy. Based on the distinctive antitumour properties of NDV and its positive interaction with the patient''s immune system, this biologic could be considered a major breakthrough in cancer treatment. On one hand, NDV infection creates an inflammatory environment in the tumour microenvironment, which can directly activate NK cells, monocytes, macrophages and dendritic cells and promote the recruitment of immune cells. On the other hand, NDV can induce the upregulation of immune checkpoint molecules, which may break immune tolerance and immune checkpoint blockade resistance. In fact, clinical data have shown that NDV combined with immune checkpoint blockade can effectively enhance the antitumour response, leading to the regression of local tumours and distant tumours when injected, and this effect is further enhanced by targeted manipulation and modification of the NDV genome. At present, recombinant NDV and recombinant NDV combined with immune checkpoint blockers have entered different stages of clinical trials. Based on these studies, further research on NDV is warranted.     

Mode of binding of quercetin to DNA

The difference spectrum of the quercetin—DNA complex versusquercetin alone was characterized by a peak at 395 nm. An increasein the magnitude of difference spectrum was seen with increasedionic strength. Spectrophotometric changes in absorbance andfluorescence of quercetin showed that ethidium bromide is ableto displace quercetin from the quercetin — DNA complex.These results indicate that the binding of quercetin to DNAdoes not involve electrostatic interactions but may be intercalativein nature. Experiments using DNase I footprinting techniqueshowed that the flavonoid does not possess any preferred sitesof binding in DNA. Strand scission in DNA by the quercetin—Cu(II)system gave a generally uniform cutting pattern of internucleotidebonds. This led to the observation that the quercetin—Cu(II)cleavage reaction has the potential of being used as preferredDNA footprinting reagent. ⁴To whom correspondence should be addressed