Inhibition of Src reduces gemcitabine-induced cytotoxicity in human pancreatic cancer cell lines.
In the present study, we examined the role of Src in gemcitabine-induced cell growth suppression in human pancreatic cancer cell lines. In two human pancreatic cancer cell lines, PK-9 and MIA PaCa-2, we found that a selective Src protein tyrosine kinase inhibitor, PP2, inhibited gemcitabine-induced cell growth suppression. When dominant negative src cDNA was constitutively expressed in PK-9 cells (PK-9-Src-DN), the degree of gemcitabine-induced cell growth suppression was decreased compared with that of mock-transfected PK-9 cells. The mechanism of the inhibitory effect of gemcitabine-induced cytotoxicity was found to be the suppression of apoptosis, which was downregulated in PK-9-Src-DN cells. These results indicate that Src mediates signals that culminate in suppressing cell growth and survival in the presence of gemcitabine, at least in particular cell lines.
Ichihara
Naoto
N
Department of Laboratory Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Kubota
Yoshitsugu
Y
Kitanaka
Akira
A
Tanaka
Terukazu
T
Taminato
Tomohiko
T
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D006801:Humans; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D044967:Serum / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014162:Transfection; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000093542:Gemcitabine
C412373:AG 1879; D000964:Antimetabolites, Antineoplastic; D003470:Culture Media; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D003841:Deoxycytidine; D019061:src-Family Kinases; D000093542:Gemcitabine