In vitro effects of lapatinib with gemcitabine for pancreatic cancer cells.
OBJECTIVE
We investigated whether lapatinib plus gemcitabine has synergistic or antagonistic effects on the pancreatic cancer cell lines MiaPaca-2 and PANC-1. Furthermore, the changes of gemcitabine sensitivity-related genes by lapatinib treatment were examined.


METHODS
The effects of lapatinib, gemcitabine, and combined treatment with both agents on cell viability were examined by methyl thiazolyl tetrazolium analysis. Synergy between lapatinib and gemcitabine was assessed by median effect analysis. The mRNA amounts of human equilibrative nucleoside transporter (hENT1), deoxycytidine kinase (dCK) and ribonucleotide reductase subunit M1 (RRM1) genes were measured by quantitative real-time polymerase chain reaction in cells exposed to lapatinib for 48 h, as compared with untreated cells.


RESULTS
No synergistic effects were observed with combined treatment in either cell line. In contrast, antagonistic effects occurred on MiaPaca-2 cells with the two agents. Specific changes in gemcitabine sensitivity-related genes induced by lapatinib were not detected in either MiaPaca-2 or PANC-1.


CONCLUSIONS
Lapatinib may not enhance the anti-tumor effects of gemcitabine for pancreatic cancer.
Akihiro
A
Murata
Bunzo
B
Nakata
Masahiro
M
Komoto
Keiichiro
K
Hirata
Kenjiro
K
Kimura
Ryosuke
R
Amano
Kosei
K
Hirakawa
D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003842:Deoxycytidine Kinase / Q000235:genetics; D004357:Drug Synergism; D033721:Equilibrative Nucleoside Transporter 1 / Q000235:genetics; D006801:Humans; D000077341:Lapatinib; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011799:Quinazolines / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000032:analysis; D012262:Ribonucleoside Diphosphate Reductase; D025521:Tumor Suppressor Proteins / Q000235:genetics; D000093542:Gemcitabine
D033721:Equilibrative Nucleoside Transporter 1; D011799:Quinazolines; D012333:RNA, Messenger; C438649:SLC29A1 protein, human; D025521:Tumor Suppressor Proteins; D000077341:Lapatinib; D003841:Deoxycytidine; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D003842:Deoxycytidine Kinase; D000093542:Gemcitabine