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.

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.

EXPRESSION OF MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN IN HUMAN GASTRIC AND RENAL CARCINOMAS

Objective The clinical signilicance of exPression of multidrug resistance- associated protein (MRP) in gastric and renal carcinoma was investigated. Methods LSAB immunohistochemistry was performed to detect eopression of MRP in the carcinoma tissues of 52 patients with gastric carcinoma and 20 cases with renal cell carcinoma. Results The positive expression rate of MRP was 38.5% (20/52) in gastric carcinoma tissues, and 60% (12/20) in renal carcinoma tissues. The expression of MRP both on cellular membrane and in cytoplasm was observed, but the expression in cytoplasm (thick granule) was more obvious. The positive expression rates of MRP in advanced gastric and renal carcinoma (Ⅲ orⅣ stage) were 60% (15/25) and 88.90% (8/9) reSPectively, which were higher than those in early lesion (Ⅰ or Ⅱ stage, 18.5% and 36.4% respectively). Furthermore, the patients with positive expression of MRP in gastric carcinoma tissues had shorter mean survival time and lower 5-year survival rate than that with negative eopression of MRP. Conclusion MRP plays an important role in the infiltration and metastasis of gastric and renal carcinoma and might contribute to the intrinsic drug - resistance in both carcinomas.

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.

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.

Expression of multidrug resistance proteins in retinoblastoma

AIM： To elucidate the mechanism of multidrug resistance in retinoblastoma, and to acquire more insights into in vivo drug resistance.METHODS： Three anticancer drug resistant Y79 human RB cells were generated against vincristine, etoposide or carboplatin, which are used for conventional chemotherapy in RB. Primary cultures from enucleated eyes after chemotherapy（PCNC） were also prepared. Their chemosensitivity to chemotherapeutic agents（vincristine, etoposide and carboplatin） were measured using MTT assay. Western blot analysis was performed to evaluate the expression of p53, Bcl-2 and various multidrug resistant proteins in retinoblastoma cells.RESULTS： Following exposure to chemotherapeutic drugs, PCNC showed less sensitivity to drugs. No significant changes observed in the p53 expression, whereas Bcl-2 expression was found to be increased in the drug resistant cells as well as in PCNC. Increased expression of P-glycoprotein（P-gp） was observed in drug resistant Y79 cells; however there was no significant change in the expression of P-gp found between primary cultures of primarily enucleated eyes and PCNC. Multidrug resistance protein 1（Mrp-1） expression was found to be elevated in the drug resistant Y79 cells as well as in PCNC. No significant change in the expression of lung resistance associatedprotein（Lrp） was observed in the drug resistant Y79 cells as well as in PCNC.CONCLUSION： Our results suggest that multidrug resistant proteins are intrinsically present in retinoblastoma which causes treatment failure in managing retinoblastoma with chemotherapy.

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.

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.

A549肺腺癌多细胞球体药敏实验、Mdr1、MRP表达以及^(99m)Tc-MIBI摄取研究

目的探讨A549肺腺癌多细胞球体的多药耐药基因(mdr1)和多药耐药相关蛋白(MRP)基因表达,甲氧基异丁基异腈(MIBI)摄取结果能否预测化疗效果。方法①血浆高峰浓度的化疗药物顺铂(DDP)、长春花碱酰胺(VDS)、氟尿嘧啶(5-氟尿嘧啶,5-FU)、羟喜树碱(HCP)、丝裂霉素(MMC)、多柔比星(阿霉素,ADM)分别进行药物敏感性实验。②单层贴壁细胞培养。96孔板1个,每组4孔,2×104细胞/孔。③MTT检测观察疗效。细胞加化疗药后培养48h,然后加MTT5mg/mL,每孔20μL,4h后用酶标仪(490nm)测量吸光度值。④RT-PCR检测A549细胞和MCF-7耐药株的mdr1和MRP表达,β2-MG作内参照。⑤96孔板内每孔一个球体,每孔掺入99mTc-MIBI9.25×104Bq(2.5μCi),分别于60和120min结束掺入并测量γ计数。结果①A549细胞药敏实验对DDP不敏感,对MMC、VDS、ADM、5-FU、HCP敏感。②MCF-7长春新碱耐药株(MCF-7/VCR)对DDP、VDS不敏感,对MMC、ADM、5-FU和HCP较敏感。③A549细胞及球体的Mdr1/β2-MG为0,MRP/β2-MG分别为0.76和0.62;MCF-7耐药细胞的mdr1/β2-MG和MRP/β2-MG分别为35和4.36。④A549多细胞球体对99mTc-MIBI120min的摄取值高于60min摄取值(P<0.05)。结论A549多细胞球体的mdr1和MRP表达水平较低以及MIBI摄取阳性提示无多药耐药性产生,与化疗药物敏感性检测结果基本一致。A549细胞对DDP耐药说明除mdr1和MRP之外,还存在与转运蛋白间接相关的其他耐药机制。

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。

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。

mrp反义RNA逆转胃癌细胞系SGC7901对VCR的耐受性

目的 :探讨以多药耐药相关蛋白 (MRP)作为靶分子进行胃癌多药耐药基因治疗的可行性。方法 :采用已构建成功的mrp反义RNA真核载体pcDNA Amrp转染胃癌细胞系SGC790 1,用G418抗性筛选出稳定细胞克隆 ,命名为M SGC790 1;用32 P标记的寡核苷酸探针打点杂交检测M SGC790 1细胞中mrpmRNA表达的变化 ;从细胞生长曲线中 ,观察M SGC790 1细胞生长速度的变化 ;经 0 .0 0 5 μg/ml的长春新碱 (VCR)处理 1月后 ,行流式细胞术检测M SGC790 1细胞周期的改变 ;同时 ,行MTT法检测M SGC790 1对VCR的IC50 值 ;最后 ,行Habit法检测M SGC790 1中谷胱苷肽S 转移酶 (GST)活性。结果 :①M SGC790 1细胞的mrpmRNA表达的阳性信号明显较对照组弱。②M SGC790 1细胞生长速度与对照组无明显差异 (P >0 .0 5 )。③M SGC790 1生长明显阻滞于S期 (P <0 .0 5 )。④M SGC790 1对VCR的IC50 值显著降低 (P <0 .0 5 )。⑤M SGC790 1中GST活性与对照组相比无明显差异 (P >0 .0 5 )。结论

MRP在非小细胞肺癌和正常肺组织中表达及其预后意义的研究

背景与目的 肿瘤多药耐药是导致肿瘤化疗失败的主要原因。多药耐药相关蛋白(MRP)在非 小细胞肺癌中的表达意义和导致耐药的机制倍受关注,其研究结果对逆转多药耐药、提高化疗疗效意义重大。 本研究旨在探讨正常肺组织和非小细胞肺癌中MRP的表达及其与患者临床病理特征和预后的关系。方法 采用SP免疫组织化学法检测62例具有完整随访资料的非小细胞肺癌组织标本中MRP的表达,并联合应 用Westernblot对30例新鲜非小细胞肺癌和相应正常肺组织中MRP的表达进行了研究。结果 正常肺组 织MRP表达水平明显低于肺癌组织(P<0.05)。MRP表达与患者性别、组织分型、细胞分化程度、淋巴结转 移均无明显关系(P>0.05)。MRP阴性表达的非小细胞肺癌患者术后生存期为69.81月±17.41月,阳性者 为25.38月±4.46月(P=0.0156)。MRP阴性的鳞癌患者术后生存期为79.86月±20.35月,阳性者为 23.41月±4.48月(P=0.015);腺癌中MRP表达与生存期无相关性。COX模型分析表明,术后生存期与淋 巴结转移(P=0.038)、MRP表达(P=0.035)呈显著负相关。结论 非小细胞肺癌的MRP表达明显高于正 常肺组织,MRP阴性的患者术后生存期明显长于阳性者,MRP表达可能是影响非小细胞肺癌预后的独立因 素。

脂多糖诱导的慢性阻塞性肺病模型大鼠肺支气管上皮MRP1功能分析

目的分析脂多糖(LPS)造模方法对慢性阻塞性肺疾病(COPD)模型大鼠的肺支气管上皮细胞多药耐药相关蛋白1(MRP1)功能的影响。方法利用LPS造模方法制备COPD模型大鼠,设置正常对照组、造模14d组和造模28 d组,分别测定其呼吸功能;以酚红外排水平评价大鼠肺支气管上皮MRP1的功能;同时采用免疫组化法分析各组大鼠肺支气管上皮MRP1的表达。结果与正常对照组比较,LPS处理组造模进程中随时间的延长大鼠的各项肺功能指标明显下降;静脉给予酚红后其BALF中酚红浓度与血浆酚红浓度的比值降低;其肺支气管上皮MRP1蛋白表达显著性降低。结论 LPS造模方法制备COPD模型大鼠,随着造模的进程,其肺支气管上皮细胞MRP1蛋白的功能随之下调。

靶向MRP1基因的shRNA稳定逆转肺癌的多药耐药性

目的:利用短发夹RNA(shRNA)表达载体逆转肺癌细胞株(A549/DDP)的多药耐药性。方法:构建2个多药耐药相关蛋白1(MRP1)基因特异的shRNA表达载体pSilencer 2.1-U6 neo-MRP1,稳定电转染A549/DDP细胞,实时荧光定量PCR分析MRP1 mRNA的表达,免疫荧光检测细胞MRP1蛋白的表达,流式细胞术检测细胞内罗丹明123(Rho123)的潴留情况。MTT法检测细胞活力。结果:成功构建了shRNA表达载体pSilencer 2.1-U6 neo-MRP1,稳定转染sh-MRP1-2.1-1和sh-MRP1-2.1-2后,A549/DDP细胞MRP1 mRNA和蛋白表达均显著降低,细胞内Rho123相对荧光强度由16.93%±0.58%分别升高至89.02%±0.59%和82.56%±1.37%;A549/DDP亲本细胞顺铂的IC50分别由(101.45±0.64)μmol/L降至(38.06±0.05)μmol/L和(53.72±0.36)μmol/L,5-氟尿嘧啶的IC50分别由(263.20±2.00)μmol/L降至(98.82±1.16)μmol/L和(141.81±0.49)μmol/L。结论:shRNA干扰表达载体pSilencer 2.1-U6 neo-RMP1能够稳定、持久地抑制MRP1基因,有效地逆转了A549/DDP细胞的多药耐药性。

五味子乙素对MRP介导的肿瘤多药耐药逆转作用的研究

目的探讨五味子乙素(SchB)对表达MRP1的肿瘤耐药细胞株的逆转耐药作用及相关机制。方法噻唑蓝(MTT)法测定不同浓度SchB对柔红霉素(DNR)抑制HL60／ADR生长及同一浓度SchB对不同化疗药物抑制HL60／ADR和HL60/MRP细胞生长的影响;流式细胞仪检测SchB作用前后,HL50／ADR和HL60／MRP细胞内化疗药物DNR和MRP1特异性底物CFDA积聚的变化。结果4～25μM Sch B作用范围内浓度依赖性下降,逆转倍数显著上升;SchB可有效降低HL60／ADR、HL60/MRP对DNR、长春新碱(VCR)和VP16的IC50,逆转倍数2倍到20倍不等;SchB能够增加DNR和MRP1特异性底物CFDA在细胞内的积聚。结论SchB对同一细胞MDR的逆转与浓度相关,在一定浓度范围内,依浓度增加而增加;SchB可以逆转不同化疗药物对MRP1介导的耐药,其逆转机制与增加化疗药物的积聚能力有关。

利福平对小鼠肝细胞胆汁酸转运体Bsep和Mrp2表达与定位的影响

目的利福平(Rifampicin,RIF)具有肝毒性,但其机制尚不清楚。本研究在RIF诱导的肝内胆汁淤积小鼠中,探讨RIF对肝细胞胆汁酸转运体胆汁酸输出泵(bile salt exportpump,Bsep)和多药抵抗相关蛋白-2(multidrug resistance-associated protein-2,Mrp2)表达和定位影响。方法 48只♀ICR小鼠随机分为4组,RIF1wk组:经灌胃给予RIF(200mg.kg-1.d-1),连续1周,于末次给药后6h取材;RIF6h组:单次灌胃给予RIF(200mg.kg-1)后6h取材;RIF1周对照组(CON1wk)与RIF6h对照组(CON6h):经灌胃给予等容积生理盐水。所有小鼠均收集血液和肝组织,常规生化检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、碱性磷酸酶(ALP)、总胆红素(TB)和结合胆红素(DB),并检测小鼠血清和肝组织总胆汁酸(TBA)水平。HE染色分析肝组织病理改变。RT-PCR测定肝脏肝细胞胆汁酸转运体Bsep和Mrp2mRNA表达。免疫荧光法分析Bsep和Mrp2在肝细胞的位置。结果给予RIF1周后,小鼠血清TB由(1.25±0.69)μmol.L-1上升至(65.73±12.08)μmol.L-1,上升近70倍,DB由(0.77±0.40)μmol.L-1上升至(53.33±12.43)μmol.L-1,上升约80倍,ALP由(110.2±13.8)U.L-1上升至(279.5±80.4)U.L-1,上升约1.5倍,TBA由(3.15±0.89)μmol.L-1上升至(13.54±6.51)μmol.L-1,上升约5倍并伴有血清ALT和AST轻度升高;肝脏组织TBA由(0.15±0.04)μmol.g-1liver上升至(0.30±0.19)μmol.g-1liver,上升约2倍;肝脏组织HE染色显示肝细胞出现脂肪变性、轻度坏死和炎症。单次给予RIF6h后血清TB、DB、ALP、ALT、AST和TBA明显上升,但未观察到小鼠肝脏组织病理发生改变。免疫荧光分析显示,给予小鼠RIF1wk与单次给予RIF6h后肝细胞中Bsep和Mrp2的定位发生了改变。而无论单次给予RIF还是连续给药1周,肝细胞Bsep和Mrp2mRNA表达水平均未发生变化。结论肝细胞胆汁酸转运体Bsep和Mrp2定位改变可能是RIF诱发肝内胆汁淤积的重要机制。

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 .

LRP与MRP在乳腺癌组织中的表达及意义

目的研究乳腺癌组织中肺耐药蛋白(LRP)、多药耐药相关蛋白(MRP)的表达及其意义。方法应用流式细胞术检测51例乳腺癌组织中LRP及MRP的表达情况,分析其与患者年龄、肿瘤大小、腋窝淋巴结转移及雌激素受体(ER)、孕激素受体(PR)表达状态等因素的关系,并探讨两者表达的相关性。结果LRP、MRP相对表达水平(用荧光强度表示)分别为0.46±0.84、1.51±1.57;除MRP与肿瘤大小相关外,两者与患者年龄、腋窝淋巴结转移、激素受体等均无相关性;乳腺癌组织中LRP与MRP表达水平间存在高度正相关(r=0.434,P=0.004)。结论部分乳腺癌具有原发性耐药,多药耐药表型隐含在乳腺癌组织中,不受化学药物的诱导,与恶性表型同时发生,且不受疾病发展的影响;MRP与肿瘤细胞增殖能力有一定关系,在肿瘤的发展过程中起重要作用;LRP似未参与乳腺癌的多药耐药机制,但与MRP在引起乳腺癌耐药方面具很大的协同性。

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。