Effect of mitoxantrone on DNA polymerase of Ehrlich ascites carcinoma cells

ｆｅｃｔｏｆｍｉｔｏｘａｎｔｒｏｎｅｏｎＤＮＡｐｏｌｙｍｅｒａｓｅｏｆＥｈｒｌｉｃｈａｓｃｉｔｅｓｃａｒｃｉｎｏｍａｃｅｌｓ１ＸＩＡＮＬｉＪｉａｎ２，ＬＩＨａｎＸｉ，ＬＩＵＺｏｎｇＣｈａｏ，ＰＡＮＱｉＣｈａｏ（ＣａｎｃｅｒＩｎｓｔｉｔｕｔｅ，...     

中间锦鸡儿新三萜甙化合物的结构研究

从中间锦鸡儿（ＣａｒａｇａｎａｉｎｔｅｒｍｅｄｉａＫ．）根部分离得到１１种化合物成分，分别为３棕榈酰β谷甾醇（３ｐａｌｍｉｔｏｙｌβｓｉｔｏｓｔｅｒｏｌ）；晁模酸（ｃｈａｕｌｍｏｇｒｉｃａｃｉｄ）；晁模酸乙酯（ｅｔｈｙｌｃｈａｕｌｍｏｏｇｒａｔｅ）；羽扇醇（ｌｕｐｅｏｌ）；胡罗卜甾醇（ｄａｕｃｏｓｔｅｒｏｌ）；三十一烷（ｈｅｎｔｒｉａｃｏｎｔａｎｅ）；α棕榈油酰甘油（αｐａｌｍｉｔｏｌｅｏｙｌｇｌｙｃｅｒｏｌ）；α棕榈酰甘油酯（αｐａｌｍｉｔｏｙｌｓｎｇｌｙｃｅｒｏｌ）；β谷甾醇（βｓｉｔｏｓｔｅｒｏｌ）；锦鸡儿甙１（ｃａｒａｇａｎｏｓｉｄｅＡ）和锦鸡儿甙２（ｃａｒａｇａｎｏｓｉｄｅＢ）。其中锦鸡儿甙１和锦鸡儿甙２为新天然产物。应用现代波谱技术（ＩＲ，ＵＶ，ＭＳ，２ＤＮＭＲ等）和化学降解方法确定了它们的化学结构     

A Novel Angular Furanocoumarin Isolated from Cnidium monnieri Fruit

从辽宁新民产蛇床Ｃｎｉｄｉｕｍｍｏｎｎｉｅｒｉ果实中分离鉴定出８个化合物，分别为２′乙酰白芷素（２′ａｃｅｔｙｌａｎｇｅｌｉｃｉｎ，８）、欧山芹素（ｏｒｏｓｅｌｏｎｅ，１）、β谷甾醇（βｓｉｔｏｓｔｅｒｏｌ，２）、哥伦比亚内酯（ｃｏｌｕｍｂｉａｎａｄｉｎ，３）、佛手柑内酯（ｂｅｒｇａｐｔｅｎ，４）、Ｏ乙酰基哥伦比亚甙元（Ｏａｃｅｔｙｌｃｏｌｕｍｂｉａｎｅｔｉｎ，５）、Ｏ乙酰异蛇床素（ｃｎｉｆｏｒｉｎＡ，６）和爱得尔庭（ｅｄｕｌｔｉｎ，７）。其中化合物８为一新化合物，化合物１系首次从该植物中分得。     

Effect of procainamide on ultrastructure of blood platelet in rabbits

ＥｆｅｃｔｏｆｐｒｏｃａｉｎａｍｉｄｅｏｎｕｌｔｒａｓｔｒｕｃｔｕｒｅｏｆｂｌｏｏｄｐｌａｔｅｌｅｔｉｎｒａｂｂｉｔｓＬＩＵＬｉａｎＰｕ，ＳＨＡＮＣｈｕｎＷｅｎ１，２，ＬＩＵＸｉＨｏｎｇ，ＸＩＡＯＨｕａｎＣａｉ，ＹＡＮＧＳｈｕＱｉｎ１（Ｄｅ...     

Phenylethanoid Glycosides from Forsythia suspensa Vahl

从连翘果实中分离了三种苯乙醇甙类化合物，ｃａｌｃｅｏｌａｒｉｏｓｉｄｅＡ（１），ｐｌａｎｔａｉｎｏｓｉｄｅＡ（２）和ｆｏｒｓｙｔｈｏｓｉｄｅＡ（３），用光谱方法鉴定了它们的结构。１和２系首次从本属植物中分离得到。通过１Ｈ１ＨＣＯＳＹ和１３Ｃ１ＨＣＯＳＹ对３的氢信号与碳信号进行正确归属，补充文献的不足。３能显著促进ＣｏｎＡ诱导的淋巴细胞转化，提示其具有增强免疫作用，该活性未见报导。     

Effect of tetrandrine on proto-oncogene c-fos expression in rat cerebrum

目的：本研究旨在探讨Ｔｅｔ对林丹—一种通过细胞内游离钙（［Ｃａ２＋］ｉ）介导大脑ｃｆｏｓ基因表达的神经毒剂—诱导的大鼠大脑ｃｆｏｓ基因表达的影响．方法：Ｎｏｒｔｈｅｒｎ印迹杂交，斑点杂交技术及双波长薄层色谱扫描分析．结果：大鼠口服林丹３０ｍｇ·ｋｇ－１１小时后大脑ｃｆｏｓ基因表达明显增强至１４６ｍｍ２，而在口服林丹前３０ｍｉｎ分别口服Ｔｅｔ１，２及４ｍｇ·ｋｇ－１，大鼠大脑ｃｆｏｓ基因表达被明显抑制（分别为８６，４０和３９ｍｍ２），其抑制程度呈剂量依赖关系．结论：Ｔｅｔ抑制Ｃａ２＋激动剂类神经毒剂—林丹诱导的大鼠大脑ｃｆｏｓ基因转录水平的表达．     

Effect of Coriaria lactone on cytosolic free calcium of cultured neurons from rat cerebral cortex

ＥｆｅｃｔｏｆＣｏｒｉａｒｉａｌａｃｔｏｎｅｏｎｃｙｔｏｓｏｌｉｃｆｒｅｅｃａｌｃｉｕｍｏｆｃｕｌｔｕｒｅｄｎｅｕｒｏｎｓｆｒｏｍｒａｔｃｅｒｅｂｒａｌｃｏｒｔｅｘ１ＺＨＵＸｉａｏＦｅｎｇ２，ＺＨＡＯＸｉＬｏｎｇ３，ＺＨＵＣｈａｎｇＧｅｎｇ（Ｄ...     

1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙胺基)丙烷盐酸盐对自发性高血压大鼠血管平滑肌细胞增殖及对PDGF-B,bFGF,c-sis,c-myc的影响

用氚胸腺嘧啶核苷（３ＨＴｄＲ）掺入法，电镜，免疫组化，原位杂交方法，在自发性高血压大鼠（ＳＨＲ）观察了１（２，６二甲基苯氧基）２（３，４二甲氧基苯乙胺基）丙烷盐酸盐（ＤＤＰＨ）对血管平滑肌细胞（ＶＳＭＣ）增殖的作用及对生长因子ＰＤＧＦＢ，ｂＦＧＦ及其相关癌基因ｃｓｉｓ与ｃｍｙｃ表达的影响。结果发现：ＤＤＰＨ在降低ＳＨＲ血压同时，能减少肾动脉ＶＳＭＣ的线粒体，粗面内质网和３ＨＴｄＲ掺入量，并能逆转ＶＳＭＣ增殖时ＰＤＧＦＢ，ｂＦＧＦ抗原及ｃｓｉｓ与ｃｍｙｃｍＲＮＡ的表达增强。提示：ＤＤＰＨ能抑制ＳＨＲ的ＶＳＭＣ增殖，与生长因子及癌基因调控的分子生物学机制有关。     

Endomorphin-1 and -2 inhibit human vascular sympathetic norepinephrine release:lack of interaction with μ_3 opiate receptor subtype

ＡＩＭ：Ｔｏｄｅｔｅｒｍｉｎｅｉｆｅｎｄｏｍｏｒｐｈｉｎ１（Ｅｎｄ１）ａｎｄ２（Ｅｎｄ２）ｉｎｔｅｒａｃｔｗｉｔｈμ３ｏｐｉａｔｅｒｅｃｅｐｔｏｒｓｕｂｔｙｐｅａｎｄｉｎｔｈｉｓｗａｙｃａｕｓｅｖａｓｃｕｌａｒｈｙｐｏｔｅｎｓｉｏｎ．ＭＥＴ...     

Five Isoflavonoid Compounds from the Roots of Caragana sinica

从豆科植物锦鸡儿Ｃａｒａｇａｎａｓｉｎｉｃａ的根（中药金雀根）中分得５个异黄酮类成分，分别鉴定为ｆｌｅｍｉｃｈａｐｐａｒｉｎＢ（１）；５羟基７甲氧基３′，４′二氧亚甲基异黄酮（２）；５羟基７，４′二甲氧基异黄酮（３）；芒柄花素ｆｏｒｍｏｎｏｎｅｔｉｎ（４）和赝靛黄素ｐｓｅｕｄｏｂａｐｔｉｇｅｎｉｎ（５）。其中化合物２为新的天然异黄酮化合物。     

The isothiocyanate produced from glucomoringin inhibits NF-kB and reduces myeloma growth in nude mice in vivo

Glucosinolates (GLs), natural compounds extracted from Brassicaceae and precursors of isothiocyanates (ITCs), have been studied in the last decades mostly due to their chemopreventive activity and, more recently, for their potential use as novel chemotherapeutics. The aim of the present study was to investigate the in vitro and in vivo activity of glucomoringin (GMG), an uncommon member of the GLs family, and to compare it with glucoraphanin (GRA), one of the most studied GL. We have evaluated the potency of both compounds in inducing cell death, cell cycle perturbations, apoptosis, NF-kB inhibition and GST-π activity in human carcinoma cells with different GST-π contents as well as in human multiple myeloma and leukaemia cell lines. GMG-derived ITC (GMG-ITC) showed to be more effective compared to GRA-derived ITC (Sulforaphane), especially in inhibiting NF-kB activity and inducing apoptosis through a caspase-dependent pathway; these effects were more pronounced in myeloma cells, in which we could also observe a long lasting growth inhibitory effect, probably due to NF-kB inhibition, which is considered essential for myeloma cell survival. Both GLs were able to induce cell death in the μM range in all tested cell lines but caused cell cycle perturbations only in myeloma cells; they were also able to modulate the GST/GSH pathway by causing a 3-fold increase in GST-π activity in MCF7 cells. In vivo study showed that pure GMG-ITC was only slightly active in a carcinoma mice model, whereas it had significant antitumoral activity in a myeloma model, causing little toxicity.     

槲皮素逆转人肝癌MDR相关基因的研究

摘 要 目的: 通过定量PCR芯片技术在基因转录水平上探讨槲皮素逆转人肝癌多药耐药( multi drug resistance, MDR)的作用机制。方法:采用体外培养人肝癌细胞Bel-7402及其耐5-氟尿嘧啶细胞Bel-FU, MTT法测定槲皮素的体外细胞毒性及浓度依赖的逆转耐药作用。定量PCR芯片检测BEL-7402细胞及Bel-FU细胞之间的差异基因,以及槲皮素作用于Bel-FU细胞前后的基因表达差异,实时定量PCR和western-blot法检测细胞中mdr1、H-ras基因以及P-gp蛋白的表达变化以验证基因芯片分析的结果。结果: 槲皮素对Bel-7402、Bel-FU细胞的IC10分别为59.2、58.2μM, IC50分别为226.7、193.9μM。16.5、33.0、49.5 μM 的槲皮素对Bel-FU 的耐药逆转倍数分别为1.14、1.68、2.38倍;与Bel-7402比较, Bel-FU细胞中的基因H-ras、Bcl-2、PDGFA、MDR1、BCRP表达上调（P＜0.05）表达上调。经槲皮素作用后,耐药细胞中基因H-ras、EGFR、FGF、VEGFA、PDGFA、MDR1、Erk1表达下调。实时定量PCR和western-blot证实了槲皮素可下调MDR1、H-ras基因以及P-gp蛋白在耐药细胞中高表达,与芯片检测到的基因水平变化一致。结论：槲皮素可逆转耐药细胞中耐药差异基因的高表达量,从而逆转人肝癌细胞的多药耐药性。     

补骨脂素逆转GST-π介导的多药耐药的研究

目的　探讨补骨脂素在逆转谷胱甘肽s-转移酶π（GST-π）介导的多药耐药中的作用,以及在MCF-7/ADR细胞中的可能机制。方法　研究时间：2015年至2020年。采用CCK-8法检测细胞活力,评价补骨脂素的细胞毒性和多药耐药逆转活性。采用实时聚合酶链反应（RT-PCR）检测GST-π的表达,检测靶基因的变化。采用免疫印迹法检测GST-π蛋白水平。采用免疫荧光法观察核因子κB（NF-κB）的活化情况。组间比较采用独立样本t检验,P<0.05为差异有统计学意义。结果　应用补骨脂素处理后,细胞内阿霉素药物浓度明显升高。与对照组相比,补骨脂素降低了治疗组GST-π在基因和蛋白水平上的表达。NF-κB抑制剂（SN50）可显著抑制乳腺癌MCF-7/ADR细胞中GST-π的表达。结论　NF-κB信号通路可能是GST-π介导的多药耐药发病机制之一。补骨脂素参与了逆转GST-π介导的多药耐药。GST-π介导的耐药机制可能与NF-κB信号通路有关,是NF-κB信号通路下游的关键因子。     

2-取代胺甲基-5(6)-(E)-取代亚甲基环戊(己)酮盐酸盐类化合物的设计、合成及其抗肿瘤活性

目的设计合成20个2,5(6)-双取代环戊(己)酮类化合物,进行抗肿瘤活性研究。方法以WB852为先导化合物,设计合成了20个2-取代胺甲基-5(6)-(E)-取代亚甲基环戊(己)酮盐酸盐类化合物。利用MTT法对其中17个化合物进行了体外细胞毒活性筛选,所用肿瘤细胞株为人乳腺癌细胞T47D、MCF-7、MCF-7/Adr;通过Habig的酶动力学方法,测试了部分目标化合物细胞外对GSTπ活性的影响。结果与结论合成了20个2-取代胺甲基-5(6)-(E)-取代亚甲基环戊(己)酮盐酸盐类化合物,其中16个为未见文献报道的新化合物,其结构均经1H-NMR、MS和IR确证。体外抗肿瘤活性筛选结果,17个化合物对3种肿瘤细胞均有不同程度的生长抑制活性,A-16、A-17、A-18、A-19等4个化合物活性显著,值得进行深入研究。9个化合物均有不同程度地抑制GSTπ的活性,其中A-4、8、9、11和15等5个化合物对GSTπ的抑制作用强于WB852。取代胺甲基部分、取代亚甲基侧链的改变以及环的大小对抗肿瘤活性和选择性影响不大,但显著影响对GSTπ的抑制作用。A-16、A-17、A-18、A-19对MCF-7/Adr的生长抑制作用与WB852相当,但均低于对MCF-7细胞的活性,对耐药细胞的活性与GSTπ抑制无关。     

Differential effects of oltipraz and its oxy-analogue on the viability of Schistosoma mansoni and the activity of glutathione S-transferase

Adult worms of Schistosoma mansoni recovered from mice treated with oltipraz (OPZ) showed a significant diminution in their ability to reduce 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) to formazan, a measure of parasite viability. Incubation of glutathione S-transferase (GST) from S. mansoni with OPZ resulted in a time- and concentration-dependent inhibition of enzyme activity. RP 36,642 (an inactive oxy-derivative of OPZ) had a minimal effect on the viability of the worms and no effect on GST activity. The structural integrity of OPZ, particularly the thione sulphur, appears to be necessary for expression of the antischistosomal effects of the drug. OPZ-induced inhibition of GST was non-competitive with either reduced glutathione (GSH) or 1-chloro-2,4-dinitrobenzene (CDNB), indicating that the drug is not a substrate for GST-catalysed conjugation reactions. In addition, the inhibition of GST could not be reversed by dialysis or repurification of the enzyme via a GSH-agarose affinity column. The effects of OPZ on GST activity could render the parasite vulnerable to damage by host-derived reactive oxygen species and aldehydic products of lipid peroxidation. The effects of OPZ on GST activity may play a role in the antischistosomal action of OPZ.     

肺癌中多药耐药因子的表达相关性及临床意义的研究

目的 探讨多药耐药因子在肺癌中表达与共表达的水平、相关性及临床意义.方法 采用免疫组化SP技术检测60例肺癌患者组织芯片中P-糖蛋白(P-gp)、多药耐药相关蛋白(MRP)、肺耐药蛋白(LRP)、谷胱苷肽-S转移酶-π(GST-π)等多药耐药因子的表达水平.结果 ①P-gp、MRP、LRP、GST-π阳性表达率分别为53.3%(32/60)、63.3%(38/60)、70.0%(42/60)、80.0%(48/60).②耐药因子在不同病理类型中表达差异有统计学意义(P＜0.05),在NSCLC中表达高于SCLC;在不同TNM分期、不同分化程度间表达差异无统计学意义(P＞0.05).③各耐药因子之间阳性共表达的结果分别为P-gp+MRP:41.6%,P-gp+LRP:35.0%,MRP+LRP:53.3%,MRP+GST-π:50.0%,LRP+GST-π:58.3%,P-gp+GST-π:45.0%,P-gp +MRP+LRP+GST-π:20.0%.其中P-gp与MRP间具有相关性(r=0.756,P＜0.01),P-gp与LRP间具有相关性(r=0.689,P＜0.01),MRP与LRP间具有相关性(r=0.669,P＜0.01),MRP与GST-π间具有相关性(r=0.546,P＜0.01),LRP与GST-π间具有相关性(r=0.848,P＜0.01),P-gp与GST-π具有相关性(r=0.535,P＜0.01).结论 肺癌的多药耐药现象是由多个耐药因子共同参与作用的结果,肺癌多药耐药的发生在肿瘤细胞的病理分型间有差异性,在不同分化程度、不同TNM分期间无差异性.

Abstract：

Objective To study the expression,co-expression, and clinical significance of four multi-drug resistance factors in lung cancer. Methods The P-glycoprotein (P-gp), mullidrug resistance-associated protein ( MRP, lung resistance protein ( LRP), glutathione-S-transferase (GST-π) of 60 lung cancer patients were detected by immunohistochemical methods. Results The positive drug resistance rate of P-gp, MRP, LRP, GST-π was 53.3% (32/60) ,63.3% (38/60) ,70.0% (42/60) ,80.0% (48/60) respectively. Patients with NSCLC had significantly higher expression of the drug resistance factors than those with SCLC. No relation was observed among the expression of drug resistance factors and TNM stage and cell differentiation. The-expression rate was as follows: Pgp + MRP :41.6%, P-gp + LRP :35.0%, MRP + LRP :53.3%, MRP + GST-π:50.0%, LRP + GST-π: 58.3%, Pgp + GST-π:45.0%. P-gp + MRP + LRP + GST-π:20.0%. Among them, significant relation was detected between P-gp and MRP ( rs = 0.756, P ＜ 0. 0 ), between P-gp and LRP ( rs = 0.689, P ＜ 0.01 ), between MRP and LRP (rs = 0.669, P ＜ 0.01 ), between MRP and GST-π( rs = 0.546, P ＜ 0.01 ), between LRP and GST-π ( rs = 0.848, P ＜0.01 ), between P-gp and LRP( rs =0.535 ,P ＜0.01 ). Conclusions The Multi-drug resistance in lung cancer patients is affected by various multidrug resistance factors. The drug resistance factors' expression is related to histology, but not to TNM stage end cell differentiation.     

三氧化二砷对胃癌细胞SGC7901/ADR GST-π和TopoⅡ表达的影响

目的探讨三氧化二砷(As2O3)对胃癌细胞SGC7901/ADR阿霉素(ADM)耐药性的逆转作用和对GSTπ和TopoⅡ表达的影响。方法用MTT法检测As2O3的非细胞毒性浓度和SGC7901/ADR细胞对ADM的敏感性,用流式细胞仪检测细胞内药物浓度及用免疫组织化学法检测细胞GSTπ和TopoⅡ的表达。结果与结论0.4~0.8μmol.L-1As2O3对耐药细胞SGC7901/ADR无明显毒性(P<0.01),As2O3可下调GSTπ表达,提高SGC7901/ADR细胞内ADM浓度,部分逆转SGC7901/ADR细胞对ADM的耐药性。     

木犀草素抑制白血病耐药株K562/A02的GST-π表达

目的 探讨木犀草素(luteolin)对白血病耐药株K562/A02细胞谷胱甘肽S转移酶π(GST-π)的影响.方法 木犀草素30 mmol/L预处理K562/A02细胞第1、3、5d后,MTT法测定阿霉素IC50,采用722分光光度计测定细胞内GSH含量及Western Blot法测定木犀草素处理后GST-π蛋白表达.结果 木犀草素对K562/A02的耐药性具有明显的逆转作用,用木犀草素处理后,对阿霉素药物敏感性的相对逆转效率第1、3、5d分别为10.7％、42.7％和15.8％;木犀草素显著降低K562/A02细胞内GSH含量,GST-π蛋白的表达于用药后第1、3、5d分别下降22％、56％和34％.结论 木犀草素具有较强的逆转K562/A02细胞多药耐药的作用,其逆转机制可能与降低细胞内GSH含量,下调K562/A02细胞GST-π蛋白的表达相关.