Influence of Chemotherapeutic Treatment on Expression of Human Multidrug Resistance Protein (ABCC, ABCB) Family Members in Pancreatic Cancer Cell Lines

Abstract

AIM: Chemotherapeutic treatment of pancreatic carcinomas is often impeded by intrinsic multidrug resistance (MDR). This MDR phenotype can be caused by transporters of the MDR P-glycoprotein (ABCB) or multidrug resistance related protein (MRP) family(ABCC). To elucidate the role of ABCB and ABCC family members in pancreatic carcinomas, we analyzed mRNA expression of MDR-1, MDR-3, MRP-1, MRP-3 and MRP-5, which have been shown to confer resistance to chemotherapeutic drugs. METHODS: mRNA expression was quantified in 10 different human pancreatic carcinoma cell lines before and during continuous in vitro chemotherapy including gemcitabine (0.5 μg/mL), 5-fluorouracil (5-FU; 0.5μg/mL), cisplatin (0.05 μg/mL) or the combination of 5-FU and cisplatin. RESULTS: Quantitative RT-PCR demonstrated high base line expression levels of MRP-3> MRP-1> MRP-5 in the pancreatic cell lines Panc-1, KCI-MOH1, MIAPaCa-2, PK-1, PK-8, PK-9 and AsPC-1, whereas PaTu8902, HuP-T4 und FAMPAC revealed low base line mRNA transcript levels. 5-FU and cisplatin caused a significant elevation of MRP-3> MRP-1> MRP-5, while gemcitabine affected the mRNA expression less. CONCLUSION: MRP-1, MRP-3 and MRP-5 are likely to be involved in the MDR phenotype. The majority of pancreatic carcinoma cells express high levels of MRPs even without prior chemotherapeutic treatment. Quantification of MRP expression may predict individual tumor responses and guide chemotherapeutic treatment.