蛇毒膜毒素抗肿瘤作用的研究进展

蛇毒膜毒素抗肿瘤作用的研究进展杨惠玲，郭禹标蛇毒含有各种酶类和多种不同生理与药理活性蛋白。自１９３６年ｓａｒｋｅｒ［１］用盐析法从眼镜蛇（Ｎａｊａｎａｊａａｔｒａ）蛇毒中分离出一个能使离体猫心停搏的毒素以来，各种类似毒素如心脏毒素（Ｃａｒｄｉｏｔｏｘ...     

白细胞介素6及其毒素融合蛋白抗肿瘤作用的研究进展

白细胞介素６（ＩＬ－６）是一种具有多种功能的细胞因子，除参与免疫调节和造血调控外，还参与了机体的抗肿瘤免疫。ＩＬ－６主要通过调动机体免疫机制发挥抗肿瘤效应，亦能直接抑制肿瘤细胞增殖，但在一定条件下能促进某些恶性肿瘤细胞增殖；ＩＬ－６毒素融合蛋白则能高选择地杀伤高表达ＩＬ－６受体（ＩＬ－６Ｒ）的肿瘤细胞。本文拟就ＩＬ－６及其毒素融合蛋白的抗肿瘤研究进展作一综述。     

石见穿活性部位的体外抗肿瘤作用研究

目的:考察石见穿不同提取部位的体外抗肿瘤活性,从而确定其体外抗肿瘤作用的活性部位。方法:使用95%工业酒精对石见穿饮片进行提取,然后分别用石油醚、乙酸乙酯、氯仿和正丁醇依次对乙醇提取部位进行分段萃取,采用MTT法（四甲基偶氮唑蓝比色试验）测定各个提取部位对体外培养的5株人肿瘤细胞的增殖抑制作用。结果:在体外,氯仿部位和乙酸乙酯部位对于5株人肿瘤细胞株具有较强的增殖抑制作用。结论:氯仿部位、乙酸乙酯部位是石见穿发挥体外抗肿瘤作用的主要活性部位。     

银环蛇毒素对白血病K562细胞株凋亡诱导作用的研究

目的 探讨银环蛇毒素及其若干组分在体外对白血病K562细胞株的凋亡诱导作用。方法 采用阳离子交换层析法分离纯化银环蛇粗毒，应用MTT法、荧光显微镜和流式细胞术等研究毒素对K562细胞株的凋亡作用。结果 除Ⅳ峰毒素外，银环蛇粗毒及分离的部分组分IV峰、Ⅶ峰和Ⅷ峰等毒素的荧光显微图末见特征性的凋亡小体，DNA含量分布组方图中的二倍体峰前末见Gl细胞群。结论 银环蛇毒对K562细胞具有杀伤作用，但并非是细胞凋亡作用，而是致细胞坏死，而粗毒中的某些组分可能具有促K562细胞凋亡作用。     

神经母细胞瘤中Schwann细胞抗肿瘤作用研究进展

神经母细胞瘤(Neuroblastoma, NB)包括两个细胞群:神经母/神经节细胞和Schwann细胞.     

肝癌细胞抗原负载树突状细胞激活CTL的抗肿瘤作用

肝癌是最常见的恶性肿瘤之一 ,世界范围内每年约有 10 0～ 12 5万人死于肝癌 ,我国是肝癌高发国家。导致肝癌发生的主要危险因素有HBV ,HCV感染及各种肝硬化等。肝癌化疗、放疗疗效差 ,虽尚有另外多种治疗方法 ,包括手术切除、化疗栓塞、瘤体内注射药物和肝移植等 ,但预后均不理想。研究表明肝癌患者机体免疫功能存在严重障碍。本课题对肝癌患者外周血树突状细胞介导的抗肿瘤功能状态进行了研究 ,现报道如下。1　材料与方法1.1　临床资料6例肝癌患者分别为我院及省肿瘤医院住院病人。年龄范围 36～ 5 6岁 ,平均年龄 4 6 .2岁 ,均经B超、…     

蛇毒抗肿瘤应用及其机制的研究进展

蛇毒对多种恶性肿瘤细胞有抑制增殖、诱导细胞凋亡和(或)抑制细胞迁移等作用,且呈剂量效应和(或)时间效应关系;此外,蛇毒还具有抗肿瘤血管生成作用。蛇毒抗肿瘤机制如下:1)通过阻断某些信号通路抑制肿瘤转移;2)通过激活死亡信号通路诱导肿瘤细胞凋亡;3)通过调节抑(促)癌基因表达或阻滞细胞周期抑制肿瘤细胞生长和增殖;4)通过抑制肿瘤细胞表达血管内皮生长因子(vascular endothelial growth factor,VEGF)而抑制肿瘤血管生成。蛇毒在抗肿瘤应用方面具有较大的发展空间。本文对近年来国内外蛇毒抗肿瘤应用相关文献资料进行整理和归纳,总结了蛇毒抗肿瘤作用及其机制,以期为蛇毒抗肿瘤成分的研究、开发和应用提供参考。      

阿诺宁的抗瘤作用研究

背景与目的：我们先前的研究证明,阿诺宁（anuoning)、bullatacin和squamocin在体外有强抗肿瘤作用,squamocin可诱导HL-60细胞凋亡。本研究目的的进一步研究阿诺宁的细胞毒作用和体内抗瘤作用。方法：体外试验用噻唑蓝还原法（MTT法）检测阿诺宁对体外培养的人结肠癌细胞（HT-29）、人鼻咽癌细胞（SUNE1和CNE2）、人肝癌细胞（bel-7402)、人乳腺癌细胞（MCF-7）和人肺腺癌细胞（GLC-82）的生长抑制作用。建立小鼠移植瘤模型,观察阿诺宁腹腔注射对小鼠肝癌（HepS)和肉瘤S-180的体内抗瘤作用。结果：体外实验表明,阿诺宁对CNE2、bel-7402、HT-29和SUNE1细胞的半数抑制浓度（IC50）依次为0.044μg/ml、0.068μg/ml、0.446μg/ml和1.617μg/ml;对MCF-7和GLC-82细胞的IC50分别为1.857μg/ml和3.481μg/ml。体风试验表明,阿诺宁15、30和60μg/kg,腹腔注射作用10天后,对小鼠肝癌的平均抑瘤率依次为36.9%、51.8%和57.9%,与对照组相比有统计学意义;对小鼠肉瘤S-180的平均抑瘤率依次为43.0%、52.1%和61.0%,与对照组相比有统计学意义。结论：阿诺宁对多种人肿瘤细胞有很强的抑制生长作用,并对小鼠移植瘤具有抗瘤作用。     

二甲双胍的抗肿瘤作用

二甲双胍作为一种廉价安全高效的糖尿病药物已应用多年,近年来研究显示其对各种肿瘤细胞都有不同程度的抑制作用。二甲双胍的抗肿瘤机制尚未完全明确,可能与糖代谢及蛋白激酶途径有关,也可能与炎症因子介导肿瘤杀伤有关。二甲双胍对不同肿瘤细胞杀伤效果不同,对其他抗肿瘤治疗也有一些辅助作用。     

5Fu—聚乳酸微球的体外释药及其抗癌效应研究

研究生物可降解抗癌药５Ｆｕ－ＰＬＡ微球的释药特点，鉴定其体外杀伤肿瘤细胞的活性。方法采用恒温振荡透析法和一阶导数紫外分光光度法测定了５Ｆｕ－ＰＬＡ微球的药物释放特性；ＭＴＴ法测定了不同时相５Ｆｕ－ＰＬＡ微球对５种肿瘤细胞株的杀伤活性。结果：５Ｆｕ－ＰＬＡ微球具有良好的缓释功能，半量释放期ｔ１／２为１０．４天。５Ｆｕ－ＰＬＡ微球对５种肿瘤细胞株均有较强的杀伤活性，且杀伤活性与作用时间和释药量呈正相关     

Antitumor Effect of Normal Intestinal Microflora on Ehrlich Ascites Tumor

In order to investigate the antitumor activity of intestinal microflora, the constitution of normal flora was examined in humans, guinea pigs and mice. It was clarified that Eubacterium, Bifidobacterium and Bacteroides were the predominant bacterial genera in humans. In addition, neither Clostridium nor Enterobacteriaceae was detected in guinea pigs and neither Clostridium nor Bifidobacterium was present in mice. Total bacterial counts in tumor-bearing mice were reduced in comparison with those in normal mice. Especially, in the ileum of tumor-bearing mice, the incidence of anaerobic bacterial genera was strikingly decreased. From the bacteria found, 59 living and killed strains isolated from intestinal microflora were examined for antitumor activity against Ehrlich ascites tumor. It was observed that 11 of the tested strains had antitumor activity. Four of these were toxic to the host, and in particular, all mice injected with Pseudomonas aeruginosa (TYM-8) died within several days. Eubacterium lentum (TYH-11), Propionibacterium acnes (TYM-28), Proteus mirabilis (TYM-7) and Serratia marcescens (TY-142), in which anti-tumor activity was recognized with living and formalin-killed bacteria, cured the tumor-bearing mice, and the culture supernatant of 5. marcescens contained apparent antitumor activity.     

多抗甲素对树突状细胞瘤苗体外抗肿瘤活性的影响

 目的 研究多抗甲素（Polyactin A,PA）对树突状细胞（Dendritic cell,DC ）瘤苗体外抗肿瘤活性的影响。 方法 用GM-CSF、IL-4、TNF-α体外诱导扩增脐血单个核细胞（CBMCs）中的DC,24h后将凋亡、坏死的HeLa、HepG2细胞分别加入CBMCs共孵育,使DC接受肿瘤细胞全抗原刺激,成为DC瘤苗,之后再加入PA刺激活化DC瘤苗,3天后以CBMCs为效应细胞（另设未加PA组为对照）,以相应的肿瘤细胞为靶细胞,用MTT法测定不同效靶比下效应细胞对HeLa、HepG2细胞的杀伤率。 结果加入PA后,CBMCs对HeLa、HepG2细胞的杀伤率显著提高,明显高于未加PA组。 结论PA可增强DC瘤苗对相应肿瘤的杀伤率。     

Anticellular and Antitumor Activity of Duocarmycins, Novel Antitumor Antibiotics

The anticellular and antitumor activities of novel antitumor antibiotics, duocarmycins (DUMs), were examined against human and murine tumor cells. DUMs consist of live compounds, A, B₁, B₂, C₁, and C₂, which possess a pharmacophore similar to that of CC-1065, a previously isolated antibiotic. Among them, DUMA exhibited ultrapotent growth-inhibitory activity with an IC₅₀ value of 6 p M against human uterine cervix carcinoma HeLa S₃ cells. DUMA and DUMB1 also inhibited the growth of adriamycin (ADM)-resistant lines of human nasopharynx carcinoma KB cells and breast carcinoma MCF-7 cells as well as their sensitive lines. DUMs inhibited the growth of s.c.-inoculated murine tumors such as B16 melanoma, sarcoma 180, M5076 sarcoma and colon 26. DUMs were also significantly effective in increasing the lifespan of i.p.-inoculated B16 melanoma-bearing mice, although their effect was marginal against other i.p.-inoculated tumors. As a whole, DUMB1 exhibited superior activity to the other four compounds. DUMB1 rapidly inhibited the incorporation of [³H]-TdR into macromolecules of HeLa S₃ cells as compared with that of [³H]UR or [³H]leucine. DNA strand breaks were detected in DUMB1 -treated HeLa S₃ cells by agarose gel electrophoresis with a contour-clamped homogeneous electric field apparatus. These results indicate that DUMs possess interesting biological activities as DNA-targeting antitumor antibiotics.     

Sonodynamically Induced Antitumor Effect of a Gallium-Porphyrin Complex, ATX-70

The Sonodynamically induced antitumor effect of a gallium-porphyrin complex, ATX-70, was evaluated in mice bearing colon 26. In order to find the optimum timing for the ultrasonic exposure after the administration of ATX-70, the ATX-70 concentrations in the plasma, skin, and tumor were measured and analyzed. Antitumor effect was estimated by measuring the tumor size. When used alone, ultrasound showed a slight antitumor effect, which became increasingly significant as the dose of ATX-70 was increased, while use of ATX-70 alone had no significant effect. At an ATX-70 dose of 2.5 mg/kg or higher, the average tumor size decreased to smaller than a half by three days after the ultrasonic exposure. This was smaller than a third of the size of the untreated tumors on the same day. From these results, it is concluded that ATX-70 significantly sensitizes tumors to ultrasound, demonstrating a synergistic antitumor effect.     

青蒿琥酯的抗肿瘤作用研究

目的：研究青蒿琥酯的抗肿瘤作用。方法：用青蒿琥酯或全铁转铁蛋白联合青蒿琥酯进行体外抗肿瘤实验，用MTT法检测青蒿琥酯对体外培养人结肠癌HCT-8细胞、人红白血病K562细胞及人乳腺癌MCF-7细胞的杀伤作用。结果：体外实验表明青蒿琥酯对上述3种人肿瘤细胞均有杀伤作用，对HCT-8、K562、MCF-7的IC50值为1．99μg／ml、1．62μg／ml、10．54μg／ml；加用1mg／ml全铁转铁蛋白处理3小时后再给予青蒿琥酯，其IC50值分别为3．54μg／ml、4．14μg／ml、11．95μg／ml。结论：青蒿琥酯钠在体外对HCT-8、K562、MCF-7等细胞有明显的杀伤作用，加用全铁转铁蛋白未明显增强对肿瘤细胞的杀伤作用。     

海胆肠提取物的抗肿瘤作用

目的 :观察海胆肠提取物的抗肿瘤活性。方法 :体外采用四唑盐 (MTT)比色法测定药物对人胃腺癌 SGC- 790 1细胞的生长抑制率。体内采用 S1 80 移植性实体瘤和腹腔积液瘤小鼠模型 ,分别腹腔注射不同剂量的海胆肠提取物 ,连续给药 10天。计算抑瘤率和生命延长率。结果 :MTT实验显示 ,海胆肠提取物对体外培养的 SGC- 790 1细胞增殖有明显的抑制作用 ,且抑制程度与浓度呈正相关。 2 0 0 mg· kg- 1 · d- 1 提取物腹腔注射给药 ,对小鼠肉瘤 S1 80 实体瘤的生长抑制率为为 33.5 8%(与对照组相比差异有显著性 ,P<0 .0 1) ;对腹腔积液瘤小鼠的生命延长率为 76 .94% (与对照组相比差异有显著性 ,P<0 .0 1)。结论 :海胆肠提取物在体内和体外都有明显的抗肿瘤作用     

Enhanced Antitumor Effect of 5'-Deoxy-5-fluorouridine by Oral Administration with l-Cysteine

When given orally in combination with l -cysteine, 5'-deoxy-5-fluorouridine (DFUR) brought about a significant reduction in the growth of adenocarcinoma 755 and a significant prolongation of life-span in mice bearing Lewis lung carcinoma without increased toxicity to the host as compared with DFUR alone, though l -cysteine alone did not show an appreciable antitnmor activity. Moreover, the combination of DFUR and l -cysteine resulted in a marked retardation of growth of human colon tumor LS174T transplanted into nude mice. Thus, the potency of DFUR was increased by l -cysteine. Pharmacokinetic studies revealed that after DFUR administration, plasma DFUR and 5-fluorouracil (5-FU) levels rapidly declined, but that, in the combination with l -cysteine, the plasma clearances of DFUR and 5-FU were slowed down considerably. In the tumor, DFUR and 5-FU levels were similar to those in the plasma. Such a prolongation of DFUR and 5-FU levels in plasma and tumor may produce the enhancement of antitumor effect seen with the combination of DFUR and l -cysteine.