[组织培养药物反应试验测定的胃癌化疗敏感性与多药耐药基因及蛋白表达的相关性]

[Correlation of chemosensitivity measured by histoculture drug response assay to expression of multidrug resistance genes and proteins in gastric cancer].

作者信息

Yuan Shu-Qiang, Zhou Zhi-Wei, Liang Yong-Ju, Fu Li-Wu, Chen Gong, Keshari Rajiv Prasad, Zhang Li-Yi

机构信息

State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, 510060, PR China.

出版信息

Ai Zheng. 2009 Apr;28(4):337-43.

PMID:19622290

Abstract

BACKGROUND AND OBJECTIVE

The therapeutic effects of chemotherapy on gastric cancer are still unsatisfactory. Predicting chemosensitivity of tumors as therapeutic guidance could help to improve the efficacy of chemotherapy. This study was to evaluate the chemosensitivity of gastric cancer to single or combined therapeutic agents by histoculture drug response assay, to evaluate the expression levels of multidrug resistance (MDR) genes and proteins and analyze their correlations to the chemosensitivity of gastric cancer.

METHODS

The inhibitory effects of single agents, including epirubicin, cisplatin (DDP), oxaliplatin, 5-fluorouracil (5-FU), taxetere, irinotecan, and combined regimens, including 5-FU, epirubicin plus DDP, 5-FU plus irinotecan, 5-FU plus oxaliplatin, and 5-FU, taxetere plus DDP, on 22 specimens of gastric cancer were evaluated by histoculture drug response assay. The mRNA and protein expression of MDR1, MRP1 and ABCG2 in gastric cancer were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry.

RESULTS

The inhibition rate of gastric cancer by 5-FU (29.8%) and sensitivity of gastric cancer to 5-FU (50.0%) were the highest among single agents; the inhibition rate of gastric cancer by 5-FU, taxetere plus DDP (59.8%) and sensitivity to 5-FU, epirubicin plus DDP (77.3%) were the highest among combined regimens; combined regimens achieved higher inhibition rate and sensitivity as compared with single agents (P<0.05). The positive rates of MDR1, MRP1, and ABCG2 mRNA were 90.9%, 54.5%, and 77.3%; the positive rates of MDR1, MRP1, and ABCG2 proteins were 36.4%, 54.5%, and 36.4%. High expression of MDR proteins in gastric cancer was related with the resistance to epirubicin (P<0.05).

CONCLUSION

High expression of MDR1, MRP1, ABCG2 proteins in gastric cancer is related with the resistance to epirubicin, which indicates that these MDR genes may play a role in conferring the drug resistance to epirubicin.

摘要

背景与目的

化疗对胃癌的治疗效果仍不尽人意。预测肿瘤的化疗敏感性作为治疗指导有助于提高化疗疗效。本研究旨在通过组织培养药物反应试验评估胃癌对单一或联合治疗药物的化疗敏感性，评估多药耐药（MDR）基因和蛋白的表达水平，并分析它们与胃癌化疗敏感性的相关性。

方法

通过组织培养药物反应试验评估表柔比星、顺铂（DDP）、奥沙利铂、5-氟尿嘧啶（5-FU）、多西他赛、伊立替康等单一药物以及5-FU、表柔比星加DDP、5-FU加伊立替康、5-FU加奥沙利铂、5-FU、多西他赛加DDP等联合方案对22例胃癌标本的抑制作用。采用逆转录-聚合酶链反应（RT-PCR）和免疫组织化学检测胃癌中MDR1、MRP1和ABCG2的mRNA和蛋白表达。

结果

单一药物中5-FU对胃癌的抑制率（29.8%）及敏感性（50.0%）最高；联合方案中5-FU、多西他赛加DDP对胃癌的抑制率（59.8%）及对5-FU、表柔比星加DDP的敏感性（77.3%）最高；联合方案较单一药物具有更高的抑制率和敏感性（P<0.05）。MDR1、MRP1和ABCG2 mRNA的阳性率分别为90.9%、54.5%和77.3%；MDR1、MRP1和ABCG2蛋白的阳性率分别为36.4%、54.5%和36.4%。胃癌中MDR蛋白的高表达与对表柔比星的耐药相关（P<0.05）。