A humanized anti-IGF-1R monoclonal antibody (R1507) and/or metformin             enhance gemcitabine-induced apoptosis in pancreatic cancer cells.
Pancreatic cancer is a disease with a dismal prognosis and treatment options             are limited. This study investigated the interaction of gemcitabine with R1507             and/or metformin and the induction of an inhibitor of apoptosis protein by this             com-bination. Pancreatic cancer cells were treated with gemcitabine, R1507 and             metformin alone or in combination. The effects of treatments were evaluated for             cell proliferation, apoptosis, and the expression of genes related to inhibition             of apoptosis and chemotherapy resistance. Combination of gemcitabine with R1507             and/or metformin additively interacted with the inhibition of cell proliferation             in human pancreatic ductal adenocarcinoma cell lines, SUIT-2 and MIAPaCa-2 with             differential gemcitabine resistance, and assessment of apoptosis demonstrated             that drug associations increased the apoptotic index in both cell lines. Treatment             with gemcitabine induced the expression of survivin and XIAP in both cell lines,             indicating the induction of chemoresistance. In conclusion, these data demonstrate             that the combination of gemcitabine with R1507 and/or metformin has an additive             effect in pancreatic cancer cell lines with differential sensitivity to gemcitabine;             however, gemcitabine may induce chemotherapy resistance.
Institute for Clinical Research, National Kyushu Cancer Center,                     Fukuoka, Japan.
Takako
T
Kawanami
Soichi
S
Takiguchi
Noriko
N
Ikeda
Akihiro
A
Funakoshi
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000276:immunology; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics; D000093542:Gemcitabine
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D003841:Deoxycytidine; D008687:Metformin; D017526:Receptor, IGF Type 1; C551399:teprotumumab; D000093542:Gemcitabine