Establishing the role of detoxifying enzymes in field-evolved resistance to various insecticides in the brown planthopper （Nilaparvata lugens） in South India

The brown planthopper （BPH）, Nilaparvata lugens （Stal）, is one of the major pests of rice throughout Asia. Extensive use of insecticides for suppressing N. lugens has resulted in the development of insecticide resistance leading to frequent control failures in the field. The aim of the present study was to evaluate resistance in the field populations of N. lugens from major rice growing states of South India to various insecticides. We also determined the activity of detoxifying enzymes （esterases [ESTs], glutathione S- transferases [GSTs], and mixed-fimction oxidases [MFOs]）. Moderate levels of resistance were detected in the field populations to acephate, thiamethoxam and buprofezin （resistance factors 1.05-20.92 fold, 4.52-14.99 fold, and 1.00-18.09 fold, respectively） as compared with susceptible strain while there were low levels of resistance to imidacloprid （resistance factor 1.23-6.70 fold） and complete sensitivity to etofenoprox （resistance factor 1.05- 1.66 fold）. EST activities in the field populations were 1.06 to 3.09 times higher than the susceptible strain while for GST and MFO the ratios varied from 1.29 to 3.41 and 1.03 to 1.76, respectively. The EST activity was found to be correlated to acephate resistance （r = 0.999, P ≥ 0.001）. The high selection pressure of organophosphate, neonicotinoid, and insect growth regulator （IGR） in the field is likely to be contributing for resistance in BPH to multiple insecticides, leading to control failures. The results obtained will be beneficial to IPM recommendations for the use of effective insecticides against BPH.

Polymorphisms of the oxidant enzymes glutathione S-transferase and glutathione reductase and their association with resistance of Plasmodium falciparum isolates to antimalarial drugs

Objective:To investigate the association between amplification of the two regulatory genes controlling glutathione(GSH) levels,glutathione reductase(PfGR) and glutathione S-transferase (PfGST) genes and sensitivity of Plasmodium falciparum(P.falciparum) isolates collected from different malaria endemic areas of Thailand to standard antimalarial drugs.Methods:A total of 70 P.falciparum isolates were collected from endemic areas of multi-drug resistance (Tak,Chantaburi and Ranong Provinces) during the year 2008-2009.The in vitro assessment of antimalarial activity of P.falciparum clones(K1- and Dd2 chloroquine resistant and 3D7- chloroquine sensitive) and isolates to chloroquine,quinine,mefloquine and arteusnate was performed based on SYBR Green modified assay.Results:68(97.14%),11(15.71%) and 28(40%) isolates respectively were classified as chloroquine-,quinine- and mefloquine-resistant isolates. With this limited number of P.falciparum isolates included in the analysis,no significant association between amplification of PfGST gene and sensitivity of the parasite to chloroquine, quinine,mefloquine and quinine was found.Based on PCR analysis,Dd2,Kl and 3D7 clones all contained only one copy of the PfGST gene.All isolates(70) also carried only one copy number of PfGST gene.There appears to be an association between amplification of PfGR gene and chloroquine resistance.The 3D7 and Dd2 clones were found to carry only one PfGR gene copy, whereas the K1 clone carried two gene copies.Conclusions:Chloroquine resistance is likely to be a consequence of multi-factors and enzymes in the GSH system may be partly involved. Larger number of parasite isolates are required to increase power of the hypothesis testing in order to confirm the involvement of both genes as well as other genes implicated in glutathione metabolism in conferring chloroquine resistance.

Anticancer Drug Resistance of HeLa Cells Transfected With Rat Glutathione S-transferase pi Gene

To establish a cytologic expressing system of rat glutathione S-transferase pi (GST-pi) cDNA for detecting the resistance of HeLa cells to anticancer drugs. Methods The assessment was made with various anticancer drugs (adriamycin, mitomycin, cisplatinum and vincristine) that showed different cytotoxicities in transfectant HeLa cells with pSV-GT containing rat GST-pi cDNA (HeLa/pSV-GT) or control pSV-neo (HeLa/pSV-neo). Expression levels of GST-pi mRNA in HeLa/pSV-GT and HeLa/pSV-neo were measured by in situ hybridization using Digoxin-labelled cDNA probe. Results HeLa/pSV-GT expressed significantly high degree of GST-pi mRNA, whereas both HeLa/pSV-neo and HeLa cells had very low expression. Cytotoxicities of HeLa/pSV-GT and HeLa/pSV-neo with 4 anticancer drugs were measured by MTT assay. Drug concentrations for yielding 50% inhibition (IC50) in HeLa/pSV-GT by adriamycin, mitomycin and cisplatinum were 70.13 靏/mL, 10.95 靏/mL and 16.52 靏/mL, respectively. In contrast, IC50 in HeLa/pSV-neo was 10.34 靏/mL, 7.48 靏/mL and 13.70 靏/mL, respectively. The cytotoxicities of vincristine on both HeLa/pSV-GT and HeLa/pSV-neo were not significantly different. Conclusions Our findings suggest that HeLa/pSV-GT containing rat GST-pi cDNA is resistant to some anticancer drugs due to overexpression of GST-pi. Also, HeLa/pSV-GT cell line could serve as a useful cytogenetic model for further research.

Correlative Expression of Glutathion S-Transferase-π and Multidrug Resistance Associated Protein in Bladder Transitional Cell Carcinoma

In order to elucidate the mechanisms of multidrug resistance (MDR) in bladder cancer, the expression of glutathione S-transferase-π (GST-π) and multidrug resistance associated protein (MRP) in tissue samples resected from 44 patients and 6 normal bladder mucosa as control was de- tected by using immunohistochemical method, and the results were analyzed by computer-assisted im- age analyzing system (IAS) to achieve semi-quantitative data. In addition, correlation between the expression of both factors was studied. The results showed that the positive expression rate of GST- π and MRP in bladder cancer was 72. 7 % (32/44) and 68. 2 % (30/44) respectively, significantly higher than those in normal bladder mucosa, being 16. 7% and 33. 3% respectively. The rate of GST-πpositive staining was increased correspondingly with tumor grade and stage elevated, being higher in recurrent tumors treated by chemotherapy, but not significantly (P>0. 05). There was no significant differences between the expression of MRP and tumors' behaviors and clinical characters. However, the results demonstrated that the correlation between the expression of both resistant fac- tors was very evident (r=0. 695, P<0. 0025). It was suggested that the activation of GST-π and MRP might occur during malignant transformation of normal mucosa, but tumors' differentiation and progression could not be the unique factors that influenced both overexpression. Chemotherapy might be another important reason. The correlation of both indicated that there was a common mech- anism regulating their expression probably, which made them play a pivotal role in chemotherapy drug resistance of bladder cancers.

Relationship between Glutathione Metabolism and TMV Resistance in Tobacco

This study was conducted to explore the relationship between glntathione metabolism and tobacco mosaic vires （TMV） resistance, using a TMV resistant tobacco cultivar Yuyan 8 and another tobacco cuhivar NC89 which has the same genetic background with Yuyan 8 as the experimental materials. Bioinformatics anal- ysis on the transcriptome data obtained from high-throughput sequencing revealed that among pathways enriched with differentially expressed genes, glntathione met- abolic pathway was found in both cultivars infected with TMV, and glntathione metabolism was enhanced in Yuyan 8. We detected the changes in the transcription of glntathione S-transferase （GST） which is a key enzyme in glutathione metabolic pathway with quantitative PER, the enzyme activity of GST and the content of glutathione （GSH） with spectmphotometry, and the expression levels of the genes that are related to TMV resistance or involved in photosynthesis. The results showed that GST gene expression, enzyme activity and GSH content were all increased by TMV infection in both cultivars, and the increments in Yuyan 8 were more significant. The expression of GST and other genes relate to TMV resistance were verified under different sulfur conditions. The results showed that the expression of these genes changed in a similar pattern in the two eultivars after TMV inoculation in both ＋ S and - S treatments, and their expression in - S treatment was slightly lower than in ＋ S treatment. The expression of the four genes related to TMV resistance （GST, PRI-a, HSP90 and Catalase-3） was up-regulated, and was higher in Yuyan 8 than in NC89 after TMV inoculation. On the contrast, the expression of the two genes involved in photosynthesis （ PsbA and Photosystem II 10 kDa polypeptide） were down-regulated, and the decrease in Yuyan 8 was less than in NC89. The results indicate that in the cultivars resistant to TMV infection, enhanced glntathione metabolism is beneficial to cellar redox balance, and the stable expression of PsbA which encodes the PSII reaction center protein DI can re- duce the damae to nhotosvnthetic system.

Expression of multidrug-resistance associated proteins in human retinoblastoma treated by primary enucleation

AIM： To reveal the expression of multidrug-resistance associated proteins： glutathione-S-transferase π（GSTπ）, P-glycoprotein（P-gp） and vault protein lung resistance protein（LRP） in retinoblastoma（RB） without any conservative treatment before primary enucleation and to correlate this expression with histopathological tumor features. METHODS： A total of 42 specimens of RB undergone primary enucleation were selected for the research. Sections from the formalin-fixed, paraffin-embedded specimens were stained with HE and immunohistochemistry to detect the expression of GSTπ, P-gp and LRP.RESULTS： GSTπ was expressed in 39/42（92.86%） RBs and in 9/9（100%） well-differentiated RBs. P-gp/GSTπ was found in 30（71.42%） of 42 RBs. Totally 9（21.43%） tumors were well differentiated and 33（78.57%） were poorly differentiated. Totally 15（35.71%） eyes had optic nerve（ON） tumor invasion, 36（85.71%） had choroidal tumor invasion, and 14（33.33%） had simultaneous choroidal and ON invasion. There was no statistically significant relationship between P-gp, GSTπ, LRP positivity and the degree of ocular layer tumor invasion and ON tumor invasion（P〉0.05）. CONCLUSION： RB intrinsically expresses GSTπ, P-gp and LRP. GSTπ expression is positive in 100% welldifferentiation ones, so in which way it is correlated with differentiation. But the other two proteins expressions are not related to tumor differentiation and to the degree of tumor invasion. GSTπ may be a new target of chemotherapy in RB.

Natural Products Modulate the Multifactorial Multidrug Resistance of Cancer

Multidrug resistance (MDR) is a critical problem in cancer chemotherapy. Cancer cells can develop resistance not only to a single cytotoxic drug, but also to entire classes of structurally and functionally unrelated compounds. Several mechanisms can mediate the development of MDR, including increased drug efflux from the cells by ABC-transporters (ABCT), activation of metabolic enzymes, and defective pathways towards apoptosis. Many plant secondary metabolites (SMs) can potentially increase sensitivity of drug-resistant cancer cells to chemotherapeutical agents. The present thesis investigates the modulation of MDR by certain medicinal plants and their active compounds. The inhibition of ABCTs (P-gp/MDR1, MRP1, BCRP) and metabolic enzymes (GST and CYP3A4), and the induction of apoptosis are useful indicators of the efficacy of a potential medicinal drug. The focus of this study was the possible mechanisms of drug resistance including: expression of resistance proteins, activation of metabolic enzymes, and alteration of the apoptosis and how to overcome their resistance effect on cancer cells. The overall goal of this review was to evaluate how commonly used medicinal plants and their main active secondary metabolites modulate multidrug resistance in cancer cells in order to validate their uses as anticancer drugs, introduce new therapeutic options for resistant cancer, and facilitate the development of their anticancer strategies and/or combination therapies. In conclusion, SMs from medicinal plants exhibit multitarget activity against MDR-related proteins, metabolic enzymes, and apoptotic signaling, this may help to overcome resistance towards chemotherapeutic drugs.

GSTP1通过调控STAT3信号通路促进乳腺癌细胞增殖与阿霉素耐药

目的 探讨谷胱甘肽S-转移酶P1(GSTP1)对人乳腺癌MCF-7细胞增殖与阿霉素耐药性的影响及其作用机制。方法 Western blotting检测野生型乳腺癌细胞MCF-7和阿霉素耐药乳腺癌细胞MCF-7/ADR中的GSTP1表达量,通过在MCF-7细胞中转染Flag-GSTP1质粒过表达GSTP1,在MCF-7/ADR细胞中转染GSTP1敲低慢病毒(shGSTP1)干扰GSTP1表达;平板克隆形成实验、CCK-8法和流式细胞术检测转染后乳腺癌细胞的增殖能力、阿霉素耐药性及凋亡水平的变化。Western blotting检测GSTP1表达水平的变化对STAT3通路激活的影响。结果 GSTP1在MCF-7细胞中表达量极低,且显著低于MCF-7/ADR细胞系。GSTP1过表达的MCF-7/ADR细胞克隆形成数量显著多于野生型MCF-7细胞(P<0.05)。过表达GSTP1显著提升了MCF-7细胞的增殖能力,而在MCF-7/ADR细胞系干扰GSTP1表达水平后显著抑制了细胞增殖能力(P<0.05)。CCK-8结果显示,在0.1、1、10、50μmol/ml不同浓度的阿霉素处理下,GSTP1表达水平与MCF-7细胞对阿霉素的耐药性呈正相关(P<0.05)。流式细胞术检测结果显示,GSTP1过表达组(Flag-GSTP1)和对照组(Flag)的凋亡率分别为(11.41±1.16)%和(21.1±1.72)%,GSTP1过表达显著抑制了阿霉素诱导的细胞凋亡(P<0.05)。Western blotting检测结果显示,GSTP1的过表达激活了STAT3信号通路,同时在MCF-7/ADR细胞系中抑制STAT3显著降低了GSTP1的表达水平(P<0.05)。结论 GSTP1通过上调STAT3表达调节乳腺癌细胞MCF-7的增殖能力和对阿霉素的耐药性。

Biochemical Characterization of Detoxifying Enzymes in Dimethoate-Resistant Strains of Melon Aphid, Aphis gossypii(Hemiptera: Aphididae)

The melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is a highly polyphagous sap sucking pest on wide varieties of crops including cotton and vegetables. It is a notorious vector of many plant viruses that are persistently and non-persistently transmitted. In nature, aphids are regulated by their natural enemies. However, chemical control remains a major management tool even though resistance to insecticides has been documented worldwide. A better understanding of mechanisms by which insecticide resistance occurs and its early detection is desirable to develop effective management strategies. The present investigation was conducted to study the development of resistance to an organophosphate (OP) compound-dimethoate, identify biochemical mechanism(s) involved in resistance and study cross-resistance to imidacloprid in laboratory selected A. gossypii strains in comparison to susceptible strains. Bioassay studies revealed that the LC50 values increased dramatically with dimethoate selection in resistant strains and the resistance ratio (RR) was 270-, 243- and 210-fold greater than that of the susceptible strains by 30th generation. Further, biochemical assays revealed enhanced activities of carboxylesterases (CarE), glutathione S-transferases (GSTs) and cytochrome P450-mediated p-Nitroanisole O-demethylase (PNOD) in resistant strains supporting their role in dimethoate detoxification. This study thus revealed that enhanced activity of detoxifying enzymes viz., CarE, GSTs and PNODs is one of the mechanisms underlying dimethoate resistance in A. gossypii collected from South India. Interestingly, the possibility of negatively correlated cross-resistance to imidacloprid was identified in three OP- resistant strains exhibiting 2.97-, 2.56- and 3.76-fold sensitivity to imidacloprid (a novel neonicotinoid). This indicated that the latter was less affected by the resistance mechanism(s) present.

Biochemical Characterization of Detoxifying Enzymes in Dimethoate-Resistant Strains of Melon Aphid, <i>Aphis gossypii</i>(Hemiptera: Aphididae)

The melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is a highly polyphagous sap sucking pest on wide varieties of crops including cotton and vegetables. It is a notorious vector of many plant viruses that are persistently and non-persistently transmitted. In nature, aphids are regulated by their natural enemies. However, chemical control remains a major management tool even though resistance to insecticides has been documented worldwide. A better understanding of mechanisms by which insecticide resistance occurs and its early detection is desirable to develop effective management strategies. The present investigation was conducted to study the development of resistance to an organophosphate (OP) compound-dimethoate, identify biochemical mechanism(s) involved in resistance and study cross-resistance to imidacloprid in laboratory selected A. gossypii strains in comparison to susceptible strains. Bioassay studies revealed that the LC50 values increased dramatically with dimethoate selection in resistant strains and the resistance ratio (RR) was 270-, 243- and 210-fold greater than that of the susceptible strains by 30th generation. Further, biochemical assays revealed enhanced activities of carboxylesterases (CarE), glutathione S-transferases (GSTs) and cytochrome P450-mediated p-Nitroanisole O-demethylase (PNOD) in resistant strains supporting their role in dimethoate detoxification. This study thus revealed that enhanced activity of detoxifying enzymes viz., CarE, GSTs and PNODs is one of the mechanisms underlying dimethoate resistance in A. gossypii collected from South India. Interestingly, the possibility of negatively correlated cross-resistance to imidacloprid was identified in three OP- resistant strains exhibiting 2.97-, 2.56- and 3.76-fold sensitivity to imidacloprid (a novel neonicotinoid). This indicated that the latter was less affected by the resistance mechanism(s) present.

山新杨谷胱甘肽S-转移酶编码基因PdbGSTU功能分析

【目的】本研究旨在通过分析山新杨谷胱甘肽S-转移酶编码基因PdbGSTU的抗病功能,为林木抗性育种提供基因资源与抗性种质。【方法】克隆PdbGSTU基因序列并对其进行生物信息学分析,利用荧光定量PCR技术分析该基因的组织特异性表达及植物激素诱导下的表达模式。利用转基因技术获得山新杨的过/抑制表达PdbGSTU基因植株,通过观察比较接种细链格孢菌后各植株叶片的表型和病斑面积,验证该基因的抗病功能;同时测定接种病原菌前后,野生型和转基因山新杨植株内过氧化氢含量和抗氧化相关酶活性。【结果】(1)山新杨PdbGSTU基因开放阅读框全长753 bp,编码氨基酸250个,对应的蛋白质相对分子质量为29.01 kDa,为稳定的酸性亲水蛋白,定位于细胞质中;系统进化分析显示,PdbGSTU蛋白与银中杨的蛋白KAJ6918316亲缘关系最近;启动子序列分析显示,PdbGSTU基因启动子序列含多种响应植物激素和逆境胁迫的顺式作用元件。(2)RT-qPCR结果显示,PdbGSTU基因在山新杨顶芽表达量最高,在其根部表达量最低,且该基因受茉莉酸甲酯、水杨酸和1-氨基环丙基-1-羧酸3种植物激素诱导,均上调表达。(3)接种细链格孢菌后,野生型和抑制表达PdbGSTU基因植株的叶片上,病斑面积分别为6.42和16.46 mm2,而过表达PdbGSTU基因的植株叶片上,少部分接种点出现明显病斑,其余接种部分仅出现褪色。【结论】PdbGSTU正向参与山新杨对细链格孢菌侵染的抵御过程,可通过清除活性氧提高杨树对病原菌的抗性。

谷胱甘肽S-转移酶与昆虫抗药性的关系

谷胱甘肽S -转移酶 (GSTs)是一种对杀虫剂产生代谢抗性的重要酶系 ,参与许多分子的解毒机制 ,并可转运一些重要的亲脂性化合物。GSTs在保护组织以抵御氧化侵害及氧化压力中起重要的作用。

棉铃虫的谷胱甘肽S-转移酶(GSTs):杀虫药剂和植物次生性物质的诱导与GSTs对杀虫药剂的代谢

棉铃虫Helicoverpaarmigera（Hubner）中肠谷胱甘肽S-转移酶（GSTs）对甲基对硫磷和灭多威的代谢能力明显高于对马来酸二乙酯（DEM）和两个混剂。LD5剂量的对硫磷和灭多威对棉铃虫3龄幼虫GSTs的活性均没有诱导增加的影响，用LD50的选择剂量仅对硫磷组GSTs活性增加15％。用含0．01％的芸香苷、2-十三烷酮和槲皮素的人工饲料饲养棉铃虫经1～4代后，GSTs活性提高4～18倍。3种植物次生性物质诱导组对灭多威和溴氰菊酯的敏感度均没有明显的变化，而槲皮素组对甲基对硫磷的敏感度则降低近一半，芸香苷和2-十三烷酮组对甲基对硫磷的敏感度略有降低。这种对甲基对硫磷敏感度的变化可能与上述GSTs活性的变化有关。

三氧化二砷逆转人肺腺癌A549/R细胞耐药及对GSTs表达的影响

目的探讨三氧化二砷(As2O3)对人肺腺癌A549/R细胞耐药的逆转及谷胱甘肽S-转移酶(GSTs)表达的变化。方法分别采用生化方法及RT-PCR方法检测GSTs活性及GST-πmRNA表达水平的变化。结果0.15μmol/LAs2O3可使A549/R细胞内阿霉素(ADM)浓度增加,其IC50值由原来的0.495μmol/L降低至0.217μmol/L,逆转倍数为2.3倍。耐药细胞中GSTs活性增高,GST-πmRNA呈过表达状态。不同浓度的As2O3作用后,GSTs活性下降(P<0.05),GST-πmRNA表达水平下调,呈浓度依赖性变化。结论As2O3可部分逆转A549/R细胞对ADM的耐药性,GST-π的改变参与其耐药机制。

非小细胞肺癌中肺耐药蛋白、酸性谷胱甘肽-S-转移酶的协同表达及其临床意义

目的 探讨肺耐药蛋白 (LRP) 和酸性谷胱甘肽- S- 转移酶 (GST-π) 在非小细胞肺癌 (NSCLC) 中的协同表达及其临床意义。方法 用SP免疫组化方法检测62例术前均未进行化疗的NSCLC组织中LRP、GST- π蛋白的表达情况。结果 在NSCLC中LRP、GST-.π蛋白表达的阳性率分别为75. 8% (47/62); 66. 1% (41/62)。LRP蛋白表达与肿瘤分化程度相关。GST -π蛋白表达与肿瘤组织类型、分化程度、有无淋巴结转移相关。LRP与 GST π阳性表达之间存在正相关关系。结论 LRP、GST -π在不同类型的NSCLC中均可表达, 但水平不同。

21种杀虫剂和3种植物次生物质对杨扇舟蛾各组织谷胱甘肽S-转移酶的抑制作用

为了比较杨扇舟蛾Clostera anachoreta(Fabricius)各组织谷胱甘肽S-转移酶(GSTs)的差异,利用分光光度酶动力学的方法,研究了21种杀虫剂和3种植物次生物质对杨扇舟蛾4个组织(中肠、脂肪体、头部和体壁)GSTs活性的体外影响。结果表明:21种杀虫剂和3种植物次生物质对杨扇舟蛾4个组织GSTs活性的抑制作用不同。毒死蜱、氟虫腈、槲皮素和单宁酸对于杨扇舟蛾头GSTs活性抑制作用最强;槲皮素和单宁酸对中肠GSTs活性的抑制作用最强;单宁酸对脂肪体GSTs活性的抑制作用最强;辛硫磷、高效氯氟氰菊酯、溴氰菊酯和硫丹对皮GSTs活性的抑制作用最强。杨扇舟蛾4个组织GSTs对杀虫剂和植物次生物质敏感性存在的这种差异,可能是由于其在同工酶组成上的差异造成的。

德国小蠊磷酸酯酶及谷胱甘肽S-转移酶生化特性的变化与抗药性的关系研究

目的了解德国小蠊的抗药性与磷酸酯酶和谷胱甘肽S-转移酶(GSTs)生化特性变化的关系,以初步揭示其抗性机制。方法参照Bessey等的方法测定磷酸酯酶活性与动力学参数Km和Vmax。参照Clark、Kao和Booth等的方法测定GSTs活性与动力学参数Km和Vmax。结果敏感品系与野生品系德国小蠊的酸性磷酸酯酶活力分别为0.98和26.95 nmol/(只.30 min),比活力分别为1.45和1.59μmol/(mg pro.30 min),Km值分别是26.14和0.89 mmol/L,Vmax值分别是3.33和0.85 nmol/(mg pro.30 min);敏感品系与野生品系德国小蠊的碱性磷酸酯酶活力为(0.03±0.00)和(0.28±0.06)nmol/(只.30 min),比活力分别为(0.33±0.00)和(0.37±0.00)μmol/(mg pro.30 min),Km值分别是70.38和61.24 mmol/L,Vmax值分别是16.20和14.00 nmol/(mg pro.30 min);敏感品系与野生品系德国小蠊GSTs活力分别是0.13和0.47 nmol/min,比活力分别为8.94和17.37 nmol/(mg pro.30 min);Km值分别是2.08和5.81 mmol/L,Vmax值分别是0.08和0.17 nmol/min。结论磷酸酯酶与GSTs在野外品系的抗性形成过程中起一定作用。

抗性和敏感小菜蛾谷胱甘肽-S-转移酶和谷胱甘肽的比较

研究了抗性和敏感小菜蛾谷胱甘肽 - S-转移酶 ( GSTs)在不同发育期的变化及有机磷类杀虫剂对虫体谷胱甘肽 ( GSH)质量摩尔浓度的影响 .结果表明 :抗性和敏感小菜蛾 GSTs比活力在各发育期中变化不大 ,但虫体 GSTs总活力随虫体生长发育而显著增加 ,在 4龄和蛹期达到最大值 .抗性小菜蛾 GSTs活力明显高于敏感小菜蛾 .甲胺磷和水胺硫磷对敏感小菜蛾幼虫 GSH影响不明显 ,但可导致抗性小菜蛾 GSH质量摩尔浓度的显著降低 .因此可以认为 ,GSTs活力增高和 GSH的结合作用应是小菜蛾对有机磷类杀虫剂抗性的重要机制 .

P-gp,ToPoⅡ和GST-π在胃癌组织中的表达及与预后的关系

目的:探讨胃癌患者中耐药基因P-糖蛋白(P-gp)、DNA拓扑异构酶Ⅱ(TopoⅡ)和谷胱苷肽-S转移酶(GST-π)的表达特点及对预后的影响.方法:用免疫组化方法检测130例胃癌组织中的P-gp,TopoⅡ及GST-π,分析其与临床病理特征的关系,并随访部分患者以研究其表达与预后的相关性.结果:在130例胃癌患者中,P-gp,TopoⅡ和GST-π表达的阳性率分别为24.62%,81.54%和75.38%.这3种耐药基因中,P-gp和GST-π与病变大小相关,病变直径>5cm患者中,其阳性率显著高于直径<5cm患者(χ2=4.56,P=0.033;χ2=5.545,P=0.020),有淋巴结转移患者P-gp的阳性表达率高于无淋巴结转移组(χ2=5.84,P=0.016),有血管侵犯患者P-gp和GST-π阳性表达率高于无血管侵犯患者(χ2=17.69,P<0.001;χ2=5.40,P=0.020),P-gp和GST-π表达为++^+++患者2a生存率明显低于-^+患者(χ2=3.964,P=0.047;χ2=4.2576,P=0.039);TopoⅡ的表达与病理类型及分化程度有关,在印戒细胞癌中表达率低于其他类型(χ2=7.29,P=0.007),且在低分化组中强阳性表达率明显低于中高分化组(χ2=7.79,P=0.005).结论:P-gp和GST-π的表达不仅与胃癌的生物学行为有关,同时也可作为判断胃癌患者预后的指标之一.耐药基因在胃癌中的表达程度及特点不同,因而有必要对其进行联合检测以判断耐药及预后情况.

P-gp,LRP和GST-π在非小细胞肺癌组织中的表达及与预后的关系

目的:探讨非小细胞肺癌(NSCLC)患者中耐药基因P-糖蛋白(P-gp),肺耐药相关蛋白(LRP)和谷胱苷肽-S转移酶(GST-π)的表达特点及对预后的影响.方法:用免疫组化方法检测168例非小细胞肺癌组织中的P-gp,LRP及GST-π表达情况并随访部分患者以研究其表达与预后的相关性.结果:在168例非小细胞肺癌患者中,P-gp,LRP和GST-π表达的阳性率分别为60.7%,64.03%和63.1%.P-gp和LRP与肿瘤组织类型有关,腺癌阳性率高于鳞癌(P<0.05);这3种耐药基因与病变大小相关,病变直径≥5 cm患者中,其阳性率高于直径<5 cm患者(P<0.05);有淋巴结转移患者P-gp和LRP的阳性表达率高于无淋巴结转移组(P<0.05);P-gp,LRP和GST-π表达为阴性患者2 a生存率高于阳性患者(P<0.05);三种耐药基因的表达与分化程度和年龄无关.结论:P-gp,LRP和GST-π的表达不仅与非小细胞肺癌的耐药情况有关,同时也可作为判断非小细胞肺癌患者预后的指标之一.耐药基因在非小细胞肺癌中的表达程度及特点不同,因而有必要对其进行联合检测以判断耐药及预后情况.