目的 研究原發(fā)性肝細胞癌及其癌周肝組織中多藥耐藥相關蛋白(MRP)基因的表達及意義。方法 用逆轉(zhuǎn)錄-聚合酶鏈反應(RT-PCR)技術(shù)檢測25例新鮮原發(fā)性肝細胞癌及其癌周肝組織中MRP mRNA的表達,用免疫組織化學技術(shù)LSAB法檢測60例肝細胞癌組織中MRP蛋白的表達,并結(jié)合流式細胞儀對體外化療藥物敏感性的檢測結(jié)果進行統(tǒng)計學分析。結(jié)果 原發(fā)性肝細胞癌組織中MRP mRNA與MRP蛋白表達陽性率分別為44.00%(11/25)和45.00%(27/60),均以中、低表達為主,明顯高于癌周肝組織中MRP mRNA和MRP蛋白的表達陽性率〔28.00%(7/25)、26.67%(16/60)〕,P<0.05; 5例復發(fā)性肝癌的MRP蛋白表達陽性率和表達強度呈增高的趨勢。在RT-PCR檢測的25例患者中,該兩項指標具有良好的一致性(P lt;0.05)。肝細胞癌在體外對化療藥物5-FU、DDP、ADM、MMC及CTX的敏感性分別為(15.80±7.63)%、(18.45±9.59)%、(17.95±7.99)%、(16.60±8.69)%和(17.40±10.14)%。MRP蛋白表達陽性者對5-FU、ADM的敏感性低于陰性者(P<0.05)。結(jié)論 MRP基因在原發(fā)性肝細胞癌組織中的表達可能在肝癌內(nèi)在性和獲得性耐藥中起重要作用,檢測MRP基因表達有助于預測化療反應和選擇合理的化療方案。
引用本文: 姚輝華,劉忠,嚴律南,林琦遠,劉智敏,權(quán)毅. 多藥耐藥相關蛋白基因在原發(fā)性肝細胞癌組織中的表達及意義. 中國普外基礎與臨床雜志, 2003, 10(6): 576-579. doi: 復制
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1. | Slovak ML,Ho JP,Bhardwaj G,et al.Localization of a novel multidrug resistanceassociated gene in the HT1080/DR4 and H69AR human tumor cell lines [J]. Cancer Res, 1993; 53(14)∶3221. |
2. | Stewart AJ,Canitrot Y,Baracchini E,et al.Reduction of expression of the multidrug resistance protein(MRP) in human tumor cells by antisense phosphorothioate oligonucleotides [J]. Biochem Pharmacol, 1996; 51(4)∶461. |
3. | 劉炳仁,楊純正,欒鳳君,等.用逆轉(zhuǎn)錄多聚酶鏈反應檢測白血病患者多藥耐藥基因的表達 [J]. 中華血液學雜志, 1995; 16(2)∶65. |
4. | Cole SP,Bhardwaj G,Gerlach JE,et al.Overexpression of a transporter gene in a multidrugresistant human lung cancer cell line [J]. Science, 1992; 258(5088)∶1650. |
5. | Breuninger LM, Paul S, Gaughan K,et al. Expression of multidrug resistanceassociated protein in NIH/3T3 cells confers multidrug resistance associated with increased drug efflux and altered intracellular drug distribution [J]. Cancer Res, 1995; 55(22)∶5342. |
6. | Nooter K,Westerman AM,Flens MJ,et al.Expression of the multidrug resistanceassociated protein(MRP) gene in human cancers [J]. Clin Cancer Res, 1995; 1(11)∶1301. |
7. | Takebayashi Y,Akiyama S,Natsugoe S,et al.The expression of multidrug resistance protein in human gastrointestinal tract carcinomas [J]. Cancer, 1998; 82(4)∶661. |
8. | Iwadate Y,Fujimoto S,Sueyoshi K,et al.Prediction of drug cytotoxicity in 9L rat brain tumor by using flow cytometry with a deoxyribonucleic acidbinding dye [J]. Neurosurgery, 1997; 40(4)∶782. |
9. | Matsunaga T, Shirasawa H, Hishiki T,et al.Expression of MRP and cMOAT in childhood neuroblastomas and malignant liver tumors and its relevance to clinical behavior [J]. Jpn J Cancer Res, 1998; 89(12)∶1276. |
10. | 傅建民,張偉,彭向紅,等.多藥耐藥相關蛋白在肝細胞性肝癌中的表達及臨床意義 [J]. 中華普通外科雜志, 1999; 14(1)∶22. |
- 1. Slovak ML,Ho JP,Bhardwaj G,et al.Localization of a novel multidrug resistanceassociated gene in the HT1080/DR4 and H69AR human tumor cell lines [J]. Cancer Res, 1993; 53(14)∶3221.
- 2. Stewart AJ,Canitrot Y,Baracchini E,et al.Reduction of expression of the multidrug resistance protein(MRP) in human tumor cells by antisense phosphorothioate oligonucleotides [J]. Biochem Pharmacol, 1996; 51(4)∶461.
- 3. 劉炳仁,楊純正,欒鳳君,等.用逆轉(zhuǎn)錄多聚酶鏈反應檢測白血病患者多藥耐藥基因的表達 [J]. 中華血液學雜志, 1995; 16(2)∶65.
- 4. Cole SP,Bhardwaj G,Gerlach JE,et al.Overexpression of a transporter gene in a multidrugresistant human lung cancer cell line [J]. Science, 1992; 258(5088)∶1650.
- 5. Breuninger LM, Paul S, Gaughan K,et al. Expression of multidrug resistanceassociated protein in NIH/3T3 cells confers multidrug resistance associated with increased drug efflux and altered intracellular drug distribution [J]. Cancer Res, 1995; 55(22)∶5342.
- 6. Nooter K,Westerman AM,Flens MJ,et al.Expression of the multidrug resistanceassociated protein(MRP) gene in human cancers [J]. Clin Cancer Res, 1995; 1(11)∶1301.
- 7. Takebayashi Y,Akiyama S,Natsugoe S,et al.The expression of multidrug resistance protein in human gastrointestinal tract carcinomas [J]. Cancer, 1998; 82(4)∶661.
- 8. Iwadate Y,Fujimoto S,Sueyoshi K,et al.Prediction of drug cytotoxicity in 9L rat brain tumor by using flow cytometry with a deoxyribonucleic acidbinding dye [J]. Neurosurgery, 1997; 40(4)∶782.
- 9. Matsunaga T, Shirasawa H, Hishiki T,et al.Expression of MRP and cMOAT in childhood neuroblastomas and malignant liver tumors and its relevance to clinical behavior [J]. Jpn J Cancer Res, 1998; 89(12)∶1276.
- 10. 傅建民,張偉,彭向紅,等.多藥耐藥相關蛋白在肝細胞性肝癌中的表達及臨床意義 [J]. 中華普通外科雜志, 1999; 14(1)∶22.