砷剂对肿瘤多药耐药细胞株作用机理的研究

三氧化二砷（As2O3）是人们观念中的剧毒物砒霜中的有效成分．它既是一种致癌剂又有一定有益的生物学作用．本实验研究证实，砷剂在非细胞毒性剂量下能降低化疗药物阿霉素（ADM）对多耐药（multi drug resistance，MDR）肿瘤细胞株K562/ADM细胞的IC50（细胞抑制率达50％时化疗药物的浓度），表明三氧化二砷具有逆转人红白血病细胞株K562/ADM细胞MDR作用．     

刺五加多糖对人白血病K562细胞作用的研究

目的:研究刺五加多糖对体外培养人白血病K562细胞有无增殖抑制和凋亡诱导作用。方法:取培养至对数生长期的K562细胞(密度为5×104/mL和1×106/mL)分别接种于96孔培养板(100μL/孔)及50mL培养瓶(1.5mL/瓶)中,加入不同浓度的刺五加多糖作用24h后,用CCK-8法检测刺五加多糖对K562细胞增殖抑制作用;荧光显微镜检测细胞凋亡。结果:不同浓度刺五加多糖(0.405、0.810、1.620、2.430、3.240mg/mL)作用K562细胞24 h,抑制率分别为16%、27%、48%、50%、55%;荧光显微镜下观察发现培养K562细胞中出现核固缩、凋亡小体。结论:刺五加多糖对体外培养K562细胞生长有明显的抑制作用,可诱导K562细胞凋亡。     

手性2,2'-联吡啶衍生物的不对称合成

联吡啶及其衍生物是一类重要的血管内皮生长因子抑制剂,根据化合物的构效关系,以含有不同取代基的吡啶作为起始原料,以不同的光学纯的α-氨基酸作为手性源,设计并合成了新型的含有手性中心的联吡啶衍生物,其结构通过1H NMR,13C NMR和HRMS进行了表征.体外抗肿瘤活性测定,选择五种不同的肿瘤细胞株HCT-8:人结肠癌细胞;Bel7402:人肝癌细胞;BGC-823:人胃癌细胞;A549:人肺腺癌细胞;A2780:人卵巢癌细胞对目标化合物的抗肿瘤活性进行了生物评价.     

砷剂对K_(562)细胞凋亡作用的基础研究

[目的]研究三氧化二砷对K562细胞凋亡的诱导.[方法]采用人红白血病细胞株K562细胞常规培养,给不同浓度的三氧化二砷,在不同的时间收获细胞,用台盼蓝排染法,DNA荧光染料Hoechst33342荧光染色法,及碘化丙啶(PI)与Hoechst33342共染计数坏死细胞的PI阳性率等方法,检测其对K562细胞的影响.[结果]三氧化二砷能够诱导K562细胞凋亡.并且呈现浓度依赖性和时间依赖性.[结论]三氧化二砷主要以诱导肿瘤细胞凋亡而表现其毒性作用.     

海洋来源真菌的抗肿瘤抗真菌活性筛选

目的：将深海来源的16株真菌经发酵培养与活性筛选,获取活性菌株以供筛选药源活性产物。分别经真菌普通培养基和人工海水培养基发酵获得样品,采用MTT法测试抗肿瘤活性,纸片法测试抗真菌活性。结果：菌株中有3株经过普通发酵培养基发酵和4株经过海水培养基发酵的样品在100μg/mL浓度下对K562细胞的抑制率大于60%;抗真菌活性测试中,仅有菌株16-02-1的发酵样品对受试白色念珠菌ATCC 10231和土曲霉W-1均呈现一定的抑制活性。结论：深海来源真菌在不同培养基中发酵获得的样品,抗肿瘤活性各不相同,经过筛选获得高活性菌株为寻找药源活性产物提供了菌株。     

用离子液体合成含氟1,3,4-噻二唑方法的探索研究

制备一种新型BrФnsted酸性离子液体[Hmim]HSO4为催化剂,来合成1,3,4-噻二唑类杂环化合物,通过简单的减压蒸馏可以实现催化剂和产物的分离。比较此方法与传统合成方法产率的不同,确定其最佳反应条件以及探讨该离子液体的重复使用性能。实验结果表明,未优化1,3,4-噻二唑的产率为68％,相对于传统的合成工艺,提高了10％（传统的合成产率为57．6％）;该反应的最佳反应时间为3h;离子液体循环使用3次,1,3,4-噻二唑类杂环化合物的产率均大于63％。     

姜黄素衍生物的合成及其抗肿瘤活性

以姜黄素、2-氯甲基吡啶和2-氯-5-氯甲基吡啶等为原料,制备了三种新型含氮杂环类姜黄素衍生物A、B和C,经核磁,质谱确定了这些目标化学物的结构,并使用MTT法对其抗肿瘤活性进行了测试.结果表明三种目标化合物均具有比5-氟尿嘧啶(5-Fu)更强的抗肿瘤活性.     

2—氨基—5—烷基—1，3，4—噻二唑类化合物合成方法研究

鉴于噻二唑化合物是当前杂环药类和农药很好的中间体,本文对其及中间体氨基硫脲进行了一系列探索,为工业路线奠定实验基础。     

2-[[3-羟苯基]亚氨基]苯酚的DPPH自由基清除活性研究

以生物电子等排体原理设计合成了2-[[3-羟苯基]亚氨基]苯酚,测试了其清除DP-PH·的活性,并分别探讨了溶剂效应和作用时间这两个因素对其清除DPPH·的影响。结果表明,目标化合物的半清除率浓度IC50小于10mg／mL,说明化合物具有良好的自由基清除活性;溶剂效应对目标化合物清除DPPH·的活性具有重要影响,在DMF中清除DPPH·的活性最优,IC50为408．5μM,在丙酮中的清除活性较差,IC50为868．54μM;目标化合物随作用时间对DPPH·的清除程度有差异,其对DPPH·的清除作用是随时间变化而缓慢进行的。     

含噻二唑杂环硫乙酰氨基芳烃Schiff的合成及抑菌活性研究

文章以2-氨基-5-巯基-1,3,4-噻二唑为起始原料,分别与氯乙酰苯胺和邻甲基氯乙酰苯胺通过三步反应得到了四种含噻二唑杂环硫乙酰氨基芳烃Schiff。并通过IR、1H NMR、MS和元素分析对化合物的结构进行了表征。生物活性实验结果表明:化合物(4b,4d)具有较强的抑菌作用。     

Ethaselen: a novel organoselenium anticancer agent targeting thioredoxin reductase 1 reverses cisplatin resistance in drug-resistant K562 cells by inducing apoptosis

It has been reported that Ethaselen shows inhibitory effects on thioredoxin reductase (TrxR) activity and human tumor cell growth. In order to find an efficient way to reverse cisplatin resistance, we investigated the reversal effects of Ethaselen on cisplatin resistance in K562/cisplatin (CDDP) cells that were established by pulse-inducing human erythrocyte leukemic cell line K562, which are fivefold more resistant to cisplatin compared to K562 cells. The morphology and growth showed that the adhesion of K562/CDDP further decreased while the cell volume increased. The proliferation of K562/CDDP is strengthened. The antitumor activities in vitro were assessed by MTT (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and combination index (CI), showing the significant synergic effects of cisplatin and Ethaselen. Focusing on apoptosis, a series of comparisons was made between K562 and K562/CDDP. Cisplatin induced higher reactive oxygen species (ROS) generation in K562 and subsequently induced the formation of mitochondrial permeability transition pores (PTPs). In addition, cisplatin increased the ratio of Bax to Bcl-2 in K562, which can influence the mitochondrial membrane permeability. PTP formation and mitochondrial membrane permeabilization eventually resulted in the release of cytochrome c and activation of the Caspase pathway. However, these effects were not clearly seen in K562/CDDP, which may be the reason for the acquired CDDP resistance. However, Ethaselen can induce a high level of ROS in K562/CDDP by TrxR activity inhibition and increased ratio of Bax to Bcl-2 in K562/CDDP by nuclear factor κB (NF-κB) suppression, which subsequently induces the release of cytochrome c in K562/CDDP. This response is partly responsible for the reversal of the cisplatin resistance in K562/CDDP cells.     

水杨醛吡啶酰胺双希夫碱及其配合物对大肠杆菌作用的微量热法研究

本文用微量热法研究两种新合成的希夫碱(Schiff base)化合物(L,CdL)对大肠杆菌的抗菌活性,得到了在两个新合成的Schiff base及其配合物作用下大肠杆菌生长代谢的产热曲线(Pt～t曲线)、“剂量响应”曲线(I-c曲线)以及半抑制浓度(IC50),从定性与定量两方面分析了水杨醛吡啶酰胺双希夫碱及其金属配合物(L,CdL)的抗菌活性及其作用特征。     

A novel thioredoxin reductase inhibitor inhibits cell growth and induces apoptosis in HL-60 and K562 cells

Human thioredoxin reductase (TrxR) system is associated with cancer cell growth and anti-apoptosis process. Effects of 1,2-[bis(1,2-benzisoselenazolone-3(2H)-ketone)]ethane (BBSKE), a novel TrxR inhibitor, were investigated on human leukemia cell lines HL-60 and K562. BBSKE treatment induced cell growth inhibition and apoptosis in both cell lines. Apoptosis induced by BBSKE is through Bcl-2/Bax and caspase-3 pathways. Ehrlich's ascites carcinoma-bearing mice were used to investigate the anti-tumor effect of BBSKE in vivo. Tumor-bearing mice treated with BBSKE showed an increase of life span with a comparable effect to cyclophosphamide (CTX). These results suggest a potential usage of BBSKE as a therapeutic agent against non-solid tumors.     

高效液相色谱法测定K562细胞对顺铂的摄取

顺铂是目前治疗癌症最有效的药物之一,测定细胞内顺铂的含量对于了解细胞摄取顺铂和顺铂发挥药效有重要作用．本研究通过MTT法检测了顺铂杀伤K562细胞的有效浓度,建立并利用高效液相色谱法（HPLC）检测了K562细胞对顺铂的摄入．结果表明K562细胞经10μg/mL顺铂处理12h后,细胞活性显著下降;细胞外有36．75％顺铂进入胞内．实验数据显示,顺铂对K562细胞的杀伤与其在胞内的累积相关．     

诱导肿瘤细胞凋亡的萘酰亚胺类化合物的筛选及意义

研究旨在通过MTT法从萘酰亚胺为母体合成的一系列化合物中,筛选出能够高效诱导肿瘤细胞凋亡的化合物C8。研究方法为选用不同组织来源的肿瘤细胞系MCF-7、Hela、U-251和SMMC-7721通过MTT比色法测定不同浓度的萘酰亚胺类化合物作用不同时间后对细胞体外培养的抑制影响。实验结果显示若干种亚胺类化合物中,只有化合物C8对上述肿瘤细胞的生长都具有明显的抑制作用,并随时间延长更为显著,其他化合物无显著性,进而推测化合物C8能够明显抑制不同组织来源的肿瘤细胞生长,并与剂量和时间呈正相关关系,具有高效诱导肿瘤细胞凋亡的作用。     

稳恒磁场对人白血病细胞K562生长抑制作用研究初报

人白血病细胞K5 6 2经3,6 ,9,12 ,2 4 ,36 ,4 8,6 0 ,72h不同时间磁场处理后,利用MTT法检测其生长活性,台盼蓝拒染法进行活细胞计数.结果表明,K5 6 2细胞经9mT稳恒磁场处理0～72h后,从12h起磁场对细胞生长有显著的抑制效应(p <0 .0 5 ) .K5 6 2细胞生长曲线结果与MTT实验具有良好的一致性.     

Homoharringtonine induces apoptosis of endothelium and down-regulates VEGF expression of K562 cells

Homoharringtonine (HHT) has currently been used successfully in the treatment of acute and chronic myeloid leukemias and has been shown to induce apoptosis of different types of leukemic cells in vitro. Emerging evidence suggests that angiogenesis may play an important role in hematological malignancies, such as leukemia. How ever, whether HHT can relieve leukemia by anti-angiogenesis is still unknown. We investigated the anti-angiogenesis potential of HHT with the human umbilical vein endothelial cell line (ECV304) and leukemic cell line (K562) in vitro. Cellular proliferation was determined by MTT assay and apoptosis was analyzed by flow cytometry. The mRNA expression of vascular endothelial growth factor (VEGF) was assessed by RT-PCR and VEGF protein production was detected by Western blot. Inhibition of cell proliferation and induction of apoptosis by HHT were discovered in ECV304 cells, and appeared in a dose- and time-dependent manner. Also, treatment with HHT caused down-regulation of VEGF mRNA expression in K562 cells in similar dose- and time-dependent manner and inhibition of VEGF protein production in K562 cells in response to the enhancing concentration of HHT. The results demonstrated that HHT could also induce apoptosis in endothelium and down-regulate VEGF expression in K562 cells. In conclusion, we believe HHT has anti-angiogenesis potential and speculate that HHT might exert its anti-leukemia effects via reduction of angiogenesis.