A humanized anti-IGF-1R monoclonal antibody (R1507) and/or metformin enhance gemcitabine-induced apoptosis in pancreatic cancer cells

被引：23
作者：
Kawanami, Takako
Takiguchi, Soichi [1 ]
Ikeda, Noriko [2 ]
Funakoshi, Akihiro [3 ,4 ]
机构：
[1] Kyushu Natl Canc Ctr, Inst Clin Res, Minami Ku, Fukuoka 8111395, Japan
[2] Kyushu Univ, Grad Sch Med Sci, Dept Internal Med & Bioregulatory Sci, Fukuoka 812, Japan
[3] Fukuoka Sanno Hosp, Fukuoka, Japan
[4] Int Univ Hlth & Welf, Fukuoka, Japan
来源：
ONCOLOGY REPORTS | 2012年 / 27卷 / 03期
关键词：
pancreatic cancer; gemcitabine resistance; R1507; metformin; apoptosis; chemoresistance; SURVIVIN EXPRESSION; GROWTH; THERAPY; INSULIN; GENE; SENSITIVITY; XENOGRAFTS; INHIBITION; RECEPTOR; CULTURE;
D O I：
10.3892/or.2011.1597
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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 combination. 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.
引用
收藏
页码：867 / 872
页数：6
相关论文
共 31 条
[1]   A role for survivin in radioresistance of pancreatic cancer cells [J].
Asanuma, K ;
Kobayashi, D ;
Furuya, D ;
Tsuji, N ;
Yagihashi, A ;
Watanabe, N .
JAPANESE JOURNAL OF CANCER RESEARCH, 2002, 93 (09) :1057-1062
[2]   Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial [J].
Burris, HA ;
Moore, MJ ;
Andersen, J ;
Green, MR ;
Rothenberg, ML ;
Madiano, MR ;
Cripps, MC ;
Portenoy, RK ;
Storniolo, AM ;
Tarassoff, P ;
Nelson, R ;
Dorr, FA ;
Stephens, CD ;
VanHoff, DD .
JOURNAL OF CLINICAL ONCOLOGY, 1997, 15 (06) :2403-2413
[3]   Antisense Inhibition of Survivin Expression as a Cancer Therapeutic [J].
Carrasco, Rosa A. ;
Stamm, Nancy B. ;
Marcusson, Eric ;
Sandusky, George ;
Iversen, Philip ;
Patel, Bharvin K. R. .
MOLECULAR CANCER THERAPEUTICS, 2011, 10 (02) :221-232
[4]  
Funakoshi A, SUIZO IN PRESS
[5]  
Furukawa T, 1996, AM J PATHOL, V148, P1763
[6]   High Expression Levels of Total IGF-1R and Sensitivity of NSCLC Cells In Vitro to an Anti-IGF-1R Antibody (R1507) [J].
Gong, Yixuan ;
Yao, Evelyn ;
Shen, Ronglai ;
Goel, Aviva ;
Arcila, Maria ;
Teruya-Feldstein, Julie ;
Zakowski, Maureen F. ;
Frankel, Stanley ;
Peifer, Martin ;
Thomas, Roman K. ;
Ladanyi, Marc ;
Pao, William .
PLOS ONE, 2009, 4 (10)
[7]   Pancreatic Cancer [J].
Hidalgo, Manuel .
NEW ENGLAND JOURNAL OF MEDICINE, 2010, 362 (17) :1605-1617
[8]   Immortal human pancreatic duct epithelial cell lines with near normal genotype and phenotype [J].
Hong, OY ;
Mou, LJ ;
Luk, C ;
Liu, N ;
Karaskova, J ;
Squire, J ;
Tsao, MS .
AMERICAN JOURNAL OF PATHOLOGY, 2000, 157 (05) :1623-1631
[9]  
IWAMURA T, 1987, JPN J CANCER RES, V78, P54
[10]   Metformin: Taking away the candy for cancer? [J].
Jalving, Mathilde ;
Gietema, Jourik A. ;
Lefrandt, Joop D. ;
de Jong, Steven ;
Reyners, Anna K. L. ;
Gans, Rijk O. B. ;
de Vries, Elisabeth G. E. .
EUROPEAN JOURNAL OF CANCER, 2010, 46 (13) :2369-2380
1234