O'Driscoll L, Walsh N, Larkin A, Ballot J, Ooi W S, Gullo G, O'Connor R, Clynes M, Crown J, Kennedy S
National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
Anticancer Res. 2007 Jul-Aug;27(4B):2115-20.
Pancreatic cancer is one of the most challenging solid organ malignancies. This is due to its aggressiveness, frequent late presentation as advanced disease and chemoresistance. A better understanding of the molecular basis of its drug resistance is needed.
In this study, the first of its kind, the expression of both MDR1 P-gp and MRP-1 protein in pancreatic tumour specimens was examined by immunohistochemistry. Expression of these drug efflux pumps was examined using semi-quantitative immunohistochemistry according to the percentage of cells within the tumour, demonstrating another staining intencity.
Overall, 93.3% of pancreatic carcinomas expressed MDR1 P-gp, approximately 31% co-expressed MRP-1 with MDR1 P-gp, while 6.7% expressed neither of these proteins.
Our results show that drug efflux pumps, in particular that of MDR1 P-gp, are frequently expressed in pancreatic cancer. While a causative role for these efflux pumps in pancreatic cancer chemoresistance cannot necessarily be concluded, the information presented here should be considered when selecting chemotherapy/drug efflux pump inhibitors for future therapies.
胰腺癌是最具挑战性的实体器官恶性肿瘤之一。这归因于其侵袭性、作为晚期疾病的频繁晚期表现以及化疗耐药性。需要更好地了解其耐药性的分子基础。
在本同类研究中,通过免疫组织化学检测胰腺肿瘤标本中MDR1 P-糖蛋白和MRP-1蛋白的表达。根据肿瘤内细胞百分比,使用半定量免疫组织化学检测这些药物外排泵的表达,显示出另一种染色强度。
总体而言,93.3%的胰腺癌表达MDR1 P-糖蛋白,约31%与MDR1 P-糖蛋白共表达MRP-1,而6.7%既不表达这两种蛋白。
我们的结果表明,药物外排泵,尤其是MDR1 P-糖蛋白,在胰腺癌中经常表达。虽然不一定能得出这些外排泵在胰腺癌化疗耐药中起因果作用的结论,但在为未来治疗选择化疗/药物外排泵抑制剂时,应考虑此处提供的信息。