EXPRESSION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP) AND ITS RELATIONSHIP WITH CLINICOPATHOLOGICAL FACTORS IN NON-SMALL CELL LUNG CANCER

Objective: To investigate the relationship between the expression of multidrug resistance-associated protein (MRP) and clinicopathological factors and prognosis. Methods: The expression of MRP in 62 cases with non-small cell lung cancer (NSCLC) was detected using immunohistochemistry method. The expression of MRP in 30 cases of NSCLC and corresponding normal lung tissues were detected using immunohistochemistry and Western Blot. Results: this study of tumor tissues confirmed the plasma membrane and/or cytoplasm locations of MRP. There was apparent difference between normal lung tissues and NSCLC in MRP. The survival analysis of 62 NSCLC showed that the mean survival time of the patients with negative MRP expression was 69.8117.41 months and that of patients with positive MRP expression, 25.384.46 months. Log-rank test suggested that the difference between them was significant (P=0.0156). It was also found that in squamous cell lung cancer the statistically significant difference between the mean survival time of patients with positive MRP expression and those with negative MRP expression (P=0.0153). Multivariate Cox model analysis suggested that the survival time was significantly related to expression of MRP (P=0.035) and lymphatic metastasis (P=0.038). Conclusion: MRP expression in NSCLC is significantly higher compared with normal lung tissues. The mean survival time of patients with negative MRP was relative longer and expression of MRP was an independent factor for prognosis.

EXPRESSION AND CLINICAL SIGNIFICANCE OF MULTIDRUG RESISTANCE GENE AND MULTIDRUG RESISTANCE-ASSOCIATEDPROTEIN GENE IN ACUTE LEUKEMIA

Objective: To evaluate the expression and clinical significance of multidrug resistance gene (mdr1) and multidrug resistance-associated protein (MRP) gene in acute leukemia. Methods: The expression of mdr1 and MRP assay in 55 patients with acute leukemia (AL) by reverse transcription polymerase chain reaction (RT-PCR). Results: The mdr1 and MRP gene expression levels in the relapsed AL and the blastic plastic phases of CML were significantly higher than those in the newly diagnostic AL and controls. The mdr1 and MRP gene expression levels in the clinical drug-resistant group were significantly higher than those in the non-drug-resistant group. The complete remission (CR) rate in patients with high mdr1 expression (14.3%) was significantly lower than that with low mdr1 expression (57.5%); similarly the CR rate in patients with high MRP level was also lower than that with low MRP level. Using both high expression of mdr1 and MRP gene as the indicator for evaluating multidrug resistance (MDR), the positive predictive value and accuracy increased in comparison with single gene high expression. Conclusion: Elevated level of mdr1 or MRP gene expression might be unfavorable prognostic factors for AL patient and may be used as an important index for predicting drug-resistance and relapse in AL patient. Measuring both mdr1 and MRP gene expression would increase accuracy and sensibility of evaluating MDR in acute leukemia.

Expression and significance of multi-drug resistance-associated protein 3 in different tumor cell lines

Objective To investigate the expression and meaning of MRP3 in different tumor cells. MethodsThe monoclonal antibody against MRP3 was used to identify the expression of MRP3 by flow cytometer in seven tumor cells and human embryo kidney cell lines 293T.And RT-PCR was used to detect the mRNA of MRP3 in eight cell lines. ResultsThe mRNA of MRP3 was expressed in three pancreatic carcinoma cell lines.MRP3 protein was observed in BxPC-3 and AsPC-1 cells. ConclusionMRP3 may express in different tumor in tissue-specific manner.BxPC-3 and AsPC-1 may serve as cellular models for in vitro studies on multidrug resistance of pancreatic carcinoma.

JNK1,JNK2,and JNK3 are involved in P-glycoprotein-mediated multidrug resistance of hepatocellular carcinoma cells

BACKGROUND:Multidrug resistance(MDR)is extremely common in hepatocellular carcinoma(HCC)and is a major problem in cancer eradication by limiting the efficacy of chemotherapy.Modulation of c-Jun NH2-terminal kinase(JNK)activation could be a new method to reverse MDR.However,the relationship between JNK activity and MDR in HCC cells is unknown.This study aimed to explore the relationship between MDR and JNK in HCC cell lines with different degrees of MDR.METHODS:A MDR human HCC cell line,SMMC-7721/ ADM,was developed by exposing parental cells to gradually increasing concentrations of adriamycin.The MTT assay was used to determine drug sensitivity.Flow cytometry was used to analyze the cell cycle distribution and to measure the expression levels of P-glycoprotein(P-gp)and MDR-related protein(MRP)-1 in these cells.JNK1,JNK2 and JNK3 mRNA expression levels were quantified by real-time PCR.Expression and phosphorylation of JNK1,JNK2,and JNK3 were analyzed by Western blotting.RESULTS:The MDR of SMMC-7721/ADM cells resistant to 0.05 mg/L adriamycin was mainly attributed to the overexpression of P-gp but not MRP1.In addition,these cells had a significant increase in percentage in the S phase,accompanied by a decrease in percentage in the G0/G1 phase,which is likely associated with a reduced ability for cell proliferation and MDR generation.We found that JNK1,JNK2,and JNK3 activities were negatively correlated with the degree of MDR in HCC cells.CONCLUSION:This study suggests that JNK1,JNK2,and JNK3 activities are negatively correlated with the degree of MDR in HCC cells.

Down-regulation of extracellular signal-regulated kinase 1/2 activity in P-glycoprotein-mediated multidrug resistant hepatocellular carcinoma cells

AIM： To study the expression and phosphorylation of extracellular signal-regulated kinase （ERK） i and ERK2 in multidrug resistant （MDR） hepatocellular carcinoma （HCC） cells.METHODS： MDR HCC cell lines, HepG2/adriamycin （ADM） and SMMC7721/ADM, were developed by exposing parental cells to stepwise increasing concentrations of ADM. MTT assay was used to determine drug sensitivity. Flow cytometry was employed to analyze cell cycle distribution and measure cell P-glycoprotein （P-gp） and multidrug resistant protein 1 （MRP1） expression levels. ERK1 and ERK2 mRNA expression lev-ls were measured by quantitative real-time PCR （QRTPCR）. Expression and phosphorylation of ERK1 and ERK2 were analyzed by Western blot.RESULTS： MTT assay showed that HepG2/ADM andSMMC7721/ADM were resistant not only to ADM, but also to multiple anticancer drugs. The P-gp expression was over 10-fold higher in HepG2/ADM cells than in HepG2 cells （8.92% ±0.22% vs 0.88% ± 0.05%, P 〈 0.001） and over 4-fold higher in SMMC7721/ADM cells than in SMMC7721 cells （7.37% ± 0.26% vs 1.74% ± 0.25%, P 〈 0.001）. However, the MRP1 expression was not significantly higher in HepG2/ADM and SMMC7721/ADM cells than in parental cells. In addition, the percentage of MDR HepG2/ADM and SMMC7721/ADM cells was significantly decreased in the G0/G1 phase and increased in the the S phase or G2/M phase. QRT-PCR analysis demonstrated that the ERK1 and ERK2 mRNA expression increased apparently in HepG2/ADM cells and decreased significantly in SMMC7721/ADM cells. Compared with the expression of parental cells, ERK1 and ERK2 protein expressions were markedly decreased in SMMC7721/ADM cells. However, ERK2 protein expression was markedly increased while ERK1 protein expression had no significant change in HepG2/ADM cells. Phosphorylation of ERK1 and ERK2 was markedly decreased in both HepG2/ADM and SMMC7721/ADM MDR cells.CONCLUSION： ERK1 and ERK2 activities are downregulated in P-gp-mediated MDR HCC cells. ERK1 or ERK2 might be a potential drug target for circumventing MDR HCC cells,

Multidrug resistance associated proteins in multidrug resistance

Multidrug resistance proteins(MRPs) are members of the C family of a group of proteins named ATP-binding cassette(ABC) transporters.These ABC transporters together form the largest branch of proteins within the human body.The MRP family comprises of 13 members,of which MRP1 to MRP9 are the major transporters indicated to cause multidrug resistance in tumor cells by extruding anticancer drugs out of the cell.They are mainly lipophilic anionic transporters and are reported to transport free or conjugates of glutathione(GSH),glucuronate,or sulphate.In addition,MRP1 to MRP3 can transport neutral organic drugs in free form in the presence of free GSH.Collectively,MRPs can transport drugs that differ structurally and mechanistically,including natural anticancer drugs,nucleoside analogs,antimetabolites,and tyrosine kinase inhibitors.Many of these MRPs transport physiologically important anions such as leukotriene C4,bilirubin glucuronide,and cyclic nucleotides.This review focuses mainly on the physiological functions,cellular resistance characteristics,and probable in vivo role of MRP1 to MRP9.

110例肺癌疗前MRP检测的临床意义

目的：检测１１０ 例疗前肺癌标本多药耐药相关蛋白（ ＭＲＰ） 的表达与预后的关系。方法：采用免疫组化法。结果：ＭＲＰ 总检出率６３ ．６ ％ （７０／１１０） ，ＳＣＬＣ、ＮＳＣＬＣ 分别为４６ ．７ ％ （７／８） 和６５ ．３ ％ （６２／９５） 。尽管鳞癌ＭＲＰ 的表达（７２ ．４ ％ ） 略高于腺癌（５８ ．３ ％ ） ， 但ＭＲＰ 的表达与病理类型、ＴＮＭ 分期及鳞癌、腺癌的分化程度无关。９０ 例接受化疗，７３ 例ＮＳＣＬＣ 中ＭＲＰ（ － ） 者及ＭＲＰ（ ＋ ～＋ ＋ ） 者中位生存期分别为１８ ．９ 个月和１２ ．６ 个月，Ｌｏｇ － Ｒａｎｋ ｔｅｓｔ 及Ｋａｐｌａｎ － Ｍｅｉｅｒ 生存曲线均示ＭＲＰ（ － ） 者较ＭＲＰ（ ＋ ～＋ ＋ ） 者有生存期优势（ Ｐ＜ ０ ．０２） ；３４ 例鳞癌中，ＭＲＰ（ － ）者生存率明显高于ＭＲＰ（ ＋ ～＋ ＋ ） 者。但ＭＲＰ 表达与腺癌预后无关。结论：ＭＲＰ 可能为鳞癌的负性预后因子。

人乳腺癌MRP基因表达与临床病理参数的关系

目的 研究多药耐受相关蛋白基因 (MRP)在人乳腺癌中的表达与临床病理参数的关系。方法 采用免疫组化技术检测 6 2例初发乳腺癌组织标本MRP表达 ,13例癌旁正常乳腺组织和 8例乳腺良性肿瘤组织作为对照。结果 三种组织阳性率分别为 :乳腺癌 72 6 % ,癌旁正常乳腺组织2 3 1% ,乳腺良性肿瘤 18 2 %。癌组织与其它两种组织相比 ,差异具有显著性 (P <0 0 5 )。乳腺癌组织MRP表达水平与提示乳腺癌疾病发展和预后的临床病理参数 ,如年龄、原发灶大小、淋巴结转移数、病理学类型和组织学分级无关 (P>0 0 5 )。结论 多药耐受表型是与乳腺癌恶性表型同时发生的一种内在本质特征 ,其表达程度不受疾病发展的影响。S P免疫组织化学方法检测临床乳腺标本具有灵敏度高、相对定量。

MRP基因与肿瘤的多药耐药性

在人肿瘤非典型性多药耐药机制的研究中发现了一个新的基因———多药耐药相关蛋白基因(MRP) .该基因位于人 1 6号染色体P1 3∶3,编码 1 531个氨基酸 .其产物为多药耐药相关蛋白(MRP) ,分子质量 1 90ku ,故又名 p1 90 .MRP属ABC超家族成员 ,主要分布在细胞的质膜上 .MRP的功能可能是在能量依赖的外排系统中发挥作用 .除了一些肿瘤细胞系外 ,MRP基因的高表达还见于一些血液系肿瘤及乳腺癌等 .MRP基因的高表达还可能与某些肿瘤的复发和预后有关 .

GST-π、ERCC1、MRP和LRP在卵巢癌组织中的表达及意义

目的探讨谷胱甘肽S-转移酶π(GST-π)、切除修复交叉互补基因(ERCC1)、多药耐药相关蛋白(MRP)及肺耐药相关蛋白(LRP)在上皮性卵巢癌组织中的表达及临床意义。方法采用免疫组织化学技术检测67例卵巢恶性肿瘤、20例卵巢良性肿瘤和16例正常卵巢组织中GST-π、ERCC1、MRP及LRP的表达状况,并对相关的临床病理因素进行分析。结果①67例卵巢癌中,GST-π、MRP和LRP阳性表达均显著高于其在卵巢良性肿瘤和正常卵巢组织中的阳性表达(P<0.05),而ERCC1的阳性表达同卵巢良性肿瘤和正常卵巢组织比较差异无统计学意义(P>0.05)。②GST-π的表达与肿瘤分化程度有关,分化越低表达越高(P<0.05);而ERCC1、MRP和LRP的阳性表达与多种临床病理因素无关(P>0.05)。结论 GST-π、ERCC1、MRP及LRP蛋白在卵巢癌的发生发展及耐药机制中发挥重要作用,联合检测对卵巢癌治疗方案的合理制定及化疗反应性的评估具有积极的临床指导意义。

MRP、GST-π、TopoⅡα和LRP在胃癌组织中的表达及意义

背景与目的:多药耐药相关蛋白(multidrugresistance-associatedprotein,MRP)、肺耐药蛋白(lungresistanceprotein,LRP)、谷胱甘肽转移酶(glutathione-S-transferase-π,GST-π)和拓扑异构酶Ⅱα(topoisomeraseⅡα,TopoⅡα)均在多药耐药中发挥重要作用。联合检测它们在胃癌组织中的表达,目前国内外报道极少。本研究旨在探讨联合检测MRP、GST-π、TopoⅡα、LRP在胃癌组织中的表达及意义。方法:应用免疫组化SP法检测MRP、GST-π、TopoⅡα、LRP在90例胃癌标本中的表达,采用χ2检验和Fisher精确检验分析它们表达的意义。结果:(1)MRP、GST-π、TopoⅡα、LRP在胃癌组织中的阳性表达率分别为88.9%、91.1%、74.4%和87.7%,均高于在正常胃粘膜组织中的表达(P<0.05)。(2)MRP、GST-π、LRP在高、中分化腺癌中的表达均高于低分化腺癌,而TopoⅡα在高、中分化腺癌中的表达低于低分化腺癌(P<0.05);此四者的表达情况在不同浸润程度及有/无淋巴结转移的胃癌组织之间均无统计学差异(P>0.05)。(3)MRP、GST-π、TopoⅡα、LRP两两间均无相关性。结论:MRP、GST-π、TopoⅡα和LRP均在胃癌原发性多药耐药中起重要作用,它们在胃癌组织中的表达与肿瘤分化程度有关,而与肿瘤浸润程度及是否有淋巴结转移无关。

MRP与肺癌分化程度、临床分期、淋巴结转移关系的Meta分析

目的从循证医学角度综合分析MRP(多药耐药相关蛋白)与肺癌分化程度、临床分期、淋巴结转移的相关性,预测肺癌化疗的预后。方法采用Meta分析对有关MRP与人肺癌分化程度、TNM分期、淋巴结转移的文献进行综合分析。结果共纳入16个研究,MRP在低分化肺癌组织中的阳性表达率是高分化组织的1.62倍[OR=1.62,95%CI(1.29,2.04)];在Ⅲ-Ⅳ期肺癌组织中的阳性表达率是Ⅰ-Ⅱ期的1.54倍[OR=1.54,95%CI(1.23,1.93)];而与有无淋巴结转移无相关性[OR=0.84,95%CI(0.55,1.27)]。结论 MRP的表达与肺癌组织的分化程度及临床分期存在一定的相关性,而与有无淋巴结转移无关,提示MRP可能成为一项判断肺癌预后的指标。

Ⅲ_A期非小细胞肺癌新辅助化疗后MRP、p53蛋白的表达与预后的关系

目的探讨ⅢA期非小细胞肺癌患者新辅助化疗疗效的病理组织学评价及MRP、p53蛋白表达水平与预后的相关性。方法分析我院73例ⅢA期非小细胞肺癌患者新辅助化疗后病理资料,检测其MRP、p53蛋白表达水平,并随访获得预后资料。结果病理组织学疗效评价有效率为54.79%。化疗疗效、MRP、p53蛋白表达水平与患者预后显著性相关。结论病理组织学评价与临床评价相结合,可以使新辅助化疗的疗效评价更为准确。MRP、p53蛋白的表达水平与新辅助化疗患者的预后相关,可以用来预测化疗疗效,指导临床化疗。

低频重复经颅磁刺激对氯化锂-匹鲁卡品慢性癫痫大鼠海马CA3区PGP、MRP1、MVP表达的影响

目的研究低频重复经颅磁刺激(rTMS)对氯化锂-匹鲁卡品慢性癫痫大鼠海马CA3区P-糖蛋白(PGP)、多药耐药相关蛋白(MRP)1及主穹隆蛋白(MVP)表达水平的影响。方法 60只大鼠随机分为对照组,模型组,假刺激组,治疗组,每组15只。采用氯化锂-匹鲁卡品腹腔注射构建癫痫大鼠模型,治疗组采用rT MS治疗,比较各组治疗过程中癫痫发作次数及CA3区PGP、MRP1及MVP的表达水平。结果治疗组癫痫发作频率低于模型组及假刺激组(P<0.05)。治疗组PGP、MRP1及MVP表达水平显著低于模型组及假刺激组(P<0.05),较对照组显著升高(P<0.05)。结论低频rTMS可抑制模型大鼠海马CA3区PGP、MRP1及MVP过度表达,低频rTMS的抗痫作用可能与之有关。

人原发性肝癌中多药耐药相关蛋白MRP的表达、耐药机制及逆转的研究进展

原发性肝癌(primary of liver)是我国常见的恶性肿瘤之一.手术切除率相对较低,术后复发率较高,许多肿瘤常规化疗效果差,预后不良,而肿瘤多药耐药性(MDR)则是肿瘤化疗失败的关键因素.多药耐药相关蛋白(multidrug associated protein,MRP)是一种介导多药耐药性的跨膜转运蛋白,能减少细胞内药物聚积,或改变药物在细胞内分布,从而影响化疗疗效及患者生存.主要针对MRP的结构和功能、在正常组织和肝癌细胞中的表达,以及多药耐药相关蛋白MRP的耐药机制和耐药性逆转等因素进行综述,以为临床提高肝癌的综合治疗水平提供理论基础.

Effects of Hypoxia on Expression of P-gp and Mutltidrug Resistance Protein in Human Lung Adenocarcinoma A549 Cell Line

To study the effects of hypoxia on the expression of P-gp and mutltidrug resistance protein in human lung adenocarcinoma A549 cell line, and to explore the probable mechanism of hypoxia in tumor cell of MDR. The expression of hypoxia inducible factor-1α, P-gp and mutltidrug resistance protein was immunohistochemically detected by culturing human lung adenocarcinoma A549 cell under hypoxia (2 % O_2) for 24 h. After interaction with adriamycin or cisplatin under hypoxia (2 % O_2) for 24 h, the cell survival rate was detected by MTT. Our results showed that the expression of hypoxia inducible factor-1α, P-gp and mutltidrug resistance protein under hypoxia were higher than the expression under normoxia, and correlations between the expression of HIF-1α and P-gp or multidrug resistance-associated protein was observed (P<0.05). The resistance of adriamycin of A549 cell was enhanced under hypoxia. It is concluded that the resistance of tumor chemotherapy is enhanced in hypoxia. The expression of HIF-1α is obviously correlated with the expression of P-gp and mutltidrug resistance protein.

Evaluation of the Mrp2-mediated flavonoid-drug interaction potential of quercetin in rats and in vitro models

Quercetin is a biologically active flavonoid that has been used as a popular health supplement.It is reported that quercetin may cause flavonoid-drug interaction mediated by P-glycoprotein,the most predominant efflux transporter.In this study,we comprehensively evaluated the potential of the pharmacokinetic interaction of quercetin mediated by multidrug resistance-associated protein 2(MRP2),another major efflux transporter.MRP2-transfected MDCKII cells and LS174T cells were used to evaluate the potential inhibition and induction of MRP2 by quercetin in vitro.To evaluate the induction effect of quercetin on Mrp2 in vivo,Mrp2 mRNA expression in rat liver,kidney,and small intestinal tissues was determined after the oral administration of quercetin(50,100,or 250 mg/kg)for seven days.Mrp2-mediated interaction potential was also evaluated by the pharmacokinetic study of phenolsulfonphthalein in rats after single or multiple doses of quercetin.Additionally,the effect of quercetin on absorption of docetaxel,a P-glycoprotein and CYP3A4 substrate,was also evaluated.Quercetin inhibited the function of MRP2 at 10μM and induced the mRNA expression of MRP2 at 50μM in vitro.Additionally,at 100 mg/kg,quercetin markedly increased Mrp2 expression in the small intestine of rats.However,there was no significant change in phenolsulfonphthalein pharmacokinetics due to single-(50,100,or 250 mg/kg)or multiple-dose(50,100,or 250 mg/kg for seven days)quercetin co-administration.By contrast,a significant interaction caused by quercetin(100 mg/kg)was observed in the absorption of docetaxel.The results suggested that although quercetin modulates the function and expression of MRP2 in vitro,it may have a low potential of Mrp2-mediated interaction and present negligible safety concerns related to the interaction.

In silico pharmacophore models to predict endogenous substrates for human multidrug resistance-associated proteins

Multidrug resistance-associated proteins （MRPs） can effiux structurally diverse drugs, drug conjugates, drug metabolites, as well as other small molecules out of the cells, and this is the main cause of producing multidrug resistance （MDR） of some anticaneer drugs. Therefore, it is crucial to uncover the molecular features of MRPs substrates in developing anti-MDR cancer therapy. In the present study, common feature pharmacophore models were developed by employing CATALYST Pharmacophore Modeling and Analysis tools using substrates of MRPs, including MRP1, -2, -3, -4, -5, -6, -8 and MRPs family, respectively. The models were validated using independent decoy sets generated in DUD-E, and the ones with best A UC （area under the curve） scores were chosen to predict endogenous substrates by screening the Human Metabolome Database （HMDB）. A number of molecules obtained by pharmacophore screening have been validated in the literatures. By comparing physical properties （ALOGP, Molecular_PolarSurfaceArea, Molecular_Volume, Molecular_Weight, Num H Acceptors, Num H Donors） and scaffold features of the screened candidates with the known substrates, we found that： 1） The two sets have consistent ALOGP, Molecule_Volume and Molecule_Weight distribution trend; 2） Substrates of MRP1 have a better lipophilicity than the other subtypes, which is consistent with the two hydrophobic centers on the MRP1 pharmacophore; 3） In the aspect of the scaffold structures, they have the identical or similar backbone fragments.

EXPRESSION OF MDRII MRP AND LRP GENES IN GASTRIC CARCINOMA AND THEIR CLINICAL SIGNIFICANCE

Objective: To explore the expression of mdrl,multidrug resistance-associated protein (MRP) and lungresistance protein (LRP) genes in human gastric cancerand their clinical significance. Methods: The mdrlmRNA was assayed by RT-PCR, the MRP and LRPwere detected by flow cytometry. Results: The positiverate of mdrl mRNA was 44.4% (12/27), and the meanMRP and LRP expression were independent uponpatient histologic type, nodal involvement, and TNMstage. The mdrl mRNA expression in patients withserosa invasion was 30.0% (6120), much lower than thatwithout serosa invasion (85.7%). Conclusion: Themultidrug resistance cells are present in primary gastriccarcinomas prior to chemotherapy, and analysis of mdrlgene, MRP, LRP may have guiding significance in thetreatment of gastric carcinoma.

Effect of Histone Deacetylase Inhibition on the Expression of Multidrug Resistance-associated Protein 2 in a Human Placental Trophoblast Cell Line

Background： Placental multidrug resistance-associated protein 2 （MRP2）, encoded by ABCC2 gene in human, plays a significant role in regulating drugs＇ transplacental transfer rates. Studies o11 placental MRP2 regulation could provide more therapeutic targets for individualized and safe pharmacotherapy during pregnancy. Currently, the roles of epigenetic mechanisms in regulating placental drug transporters are still unclear. This study aimed to investigate the effect of histone deacetylases （HDACs） inhibition on MRP2 expression in the placental trophoblast cell line and to explore whether HDAC 1/2/3 are preliminarily involved in this process. Methods： The human choriocarcinoma-derived trophoblast cell line （Bewo cells） was treated with the HDAC inhibitors-trichostatin A （TSA） at different concentration gradients of 0.5, 1.0, 3.0, and 5.0 μmol/L. Cells were harvested after 24 and 48 h treatment. Small interfering RNA （siRNA） specific for HDACI/HDAC2/HDAC3 or control siRNA was transfected into cells. Total HDAC activity was detected by colorimetric assay kits. HDAC 1/2/3/ABCC2 messenger RNA （mRNA） and protein expressions were determined by real-time quantitative polymerase chain reaction and Western-blot analysis, respectively. Immunofluorescence for MRP2 protein expression was visualized and assessed using an immunofluorescence microscopy and ImageJ software, respectively. Results： TSA could inhibit total HDAC activity and HDAC 1/2/3 expression in company with increase ofM RP2 expression in Bewo cells. Reduction of HDAC 1 protein level was noted after 24 h of TSA incubation at 1.0, 3.0, and 5.0 μmol/L （vs. vehicle group, all P 〈 0.001 ）, accompanied with dose-dependent induction of MRP2 expression （P = 0.045 for 1.0 μmol/L, P = 0.001 for 3.0 μmol/L, and P 〈 0.001 for 5.0 μmol/L）, whereas no significant diferences in MRP2 expression were noted after HDAC2/3 silencing. Fluorescent micrograph images of MRP2 protein were expressed on the cell membrane. The fluorescent intensities of MRP2 in the control, HDAC2, and HDAC3 siRNA-transfected cells weir week, and no significant differences were noticed among these three groups （all P 〉 0.05）. However, MRP2 expression was remarkably elevated in H DAC1 siRNA-transfected cells, which displayed an almost 3.19-fold changes in comparison with the control siRNA-transfected cells （P 〈 0.001 ）. Conclusions： HDACs inhibition could up-regulate placental MRP2 expression in ritzy, and HDAC 1 was probably to be involved in this process.