[Significance and reversal of MDR1/P-gp in pancreatic cancer chemotherapy].
OBJECTIVE
To delineate the mechanism of primary drug resistance in pancreatic cancer cell lines by investigating multidrug resistant gene 1 and its protein (P-gp).


METHODS
Reverse transcription PCR (RT-PCR) and immunocytochemistry (ICC) were carried out to investigate the expression of the MDR1 and P-gp in 8 pancreatic cancer cell lines. Flow cytometry was performed to detect P-gp function in SW1990 and HL60 cell lines. In addition, verapamil, combined with chemotherapeutic agents was carried out to evaluate its potential effect in pancreatic cancer cells.


RESULTS
The highest expression level of MDR1 mRNA was proven in SW1990 cell line by RT-PCR, while the absent expression was found in PCT-2. Weak MDR1 mRNA expression were found in PCT-3, PCT-4, ASPC, Cap-1, Mia-PaCa-2 and Panc-1 cell lines. ICC showed that P-gp was localized mainly in the membrane and partly in the plasma. P-gp overexpression was also present in SW1990. The accumulation of Rhodamin123 in SW1990 was significantly decreased (57.9% +/- 5.4%) compared with its expression in HL60 (99.5% +/- 3.3%) (P < 0.05). Verapamil (VPM), combined with ADM or E-ADM showed a potential effect on reversing drug resistance mediated by P-gp in pancreatic cancer chemotherapy.


CONCLUSIONS
MDR1 and its protein P-gp are indeed expressed in some extent in pancreatic cancer cell lines. VPM combined with ADM might imply a new strategy in pancreatic cancer chemotherapy.
Guo
Jun-chao
JC
Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Zhao
Yu-pei
YP
Liao
Quan
Q
Zhu
Yu
Y
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014700:Verapamil / Q000494:pharmacology*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D012333:RNA, Messenger; D004317:Doxorubicin; D014700:Verapamil