Expression and Significance of the Multidrug Resistance-Associated Protein Gene in Primary Hepatocellular Carcinomas_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

YAO Huihua ¹ , LIU Zhong ² , YAN Lnan ¹ , LIN Qiyuan ³ , LIU Zhimin ¹ , QUAN Yi ¹

Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041，China;

Corresponding author：

Keywords：

Hepatocellular carcinoma; RT-PCR; Immunohistochemistry; Multidrug resistance

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Objective To study the expression and significance of multidrug resistance-associated protein (MRP) gene in hepatocellular carcinoma (HCC). Methods Reverse transcription polymerase chain reaction (RT-PCR) assay was used to detect the expression of MRP mRNA in 25 fresh specimens of the primary HCC and its surrounding liver tissues. Immunohistochemistry LSAB technique was adopted to test MRP in 60 HCC specimens. The drug sensitivity was also tested by flow cytometry.Results The positive expression rates of MRP mRNA and MRP protein in primary HCC were 44.00%(11/25) and 45.00%(27/60) respectively. All the intensity of expression was low, but significant higer than its surrouding liver tissues (P＜0.05). The intensity and expression rate of MRP protein in 5 recurrent HCC had a tendency to increase. There was a correlation between the expression of MRP mRNA and MRP protein in 25 patients using RT-PCR and immunohistochemistry assay (P lt;0.05). Detected by flow cytometry, the average sensitivity of drugs in vitro of 60 HCC sp-cimens were 5-FU （15.80±7.63）%，DDP（18.45±9.59）%，ADM（17.95±7.99）%，MMC（16.60±8.69）% and CTX（17.40±10.14）%. Only 5FU and ADM were significantly affected by the expression of MRP protein (P lt;0.05).Conclusion The expression of MRP in primary HCC may be one of the important mechanisms of the intrinsic and acquired drug resistance in HCC. To study the expression of MRP could give a predictive value in HCC chemotherapy.

Citation： YAO Huihua,LIU Zhong,YAN Lnan,LIN Qiyuan,LIU Zhimin,QUAN Yi. Expression and Significance of the Multidrug Resistance-Associated Protein Gene in Primary Hepatocellular Carcinomas. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2003, 10(6): 576-579. doi: Copy

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1. Slovak ML,Ho JP,Bhardwaj G,et al.Localization of a novel multidrug resistanceassociated 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. 刘炳仁，杨纯正，栾凤君,等.用逆转录多聚酶链反应检测白血病患者多药耐药基因的表达 [J]. 中华血液学杂志, 1995; 16(2)∶65.
4. Cole SP,Bhardwaj G,Gerlach JE,et al.Overexpression of a transporter gene in a multidrugresistant human lung cancer cell line [J]. Science, 1992; 258(5088)∶1650.
5. Breuninger LM, Paul S, Gaughan K,et al. Expression of multidrug resistanceassociated 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 resistanceassociated 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 acidbinding 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,张伟,彭向红,等.多药耐药相关蛋白在肝细胞性肝癌中的表达及临床意义 [J]. 中华普通外科杂志, 1999; 14(1)∶22.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression and Significance of the Multidrug Resistance-Associated Protein Gene in Primary Hepatocellular Carcinomas

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