Institute for Clinical Research, National Kyushu Cancer Center, Fukuoka, Japan.
Oncol Rep. 2012 Mar;27(3):867-72. doi: 10.3892/or.2011.1597. Epub 2011 Dec 20.
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.
胰腺癌预后不良，治疗选择有限。本研究探讨了吉西他滨与 R1507 和/或二甲双胍的相互作用以及这种联合对凋亡抑制蛋白的诱导作用。单独或联合用吉西他滨、R1507 和二甲双胍处理胰腺癌细胞。评估治疗对细胞增殖、凋亡以及与凋亡抑制和化疗耐药相关基因的表达的影响。吉西他滨与 R1507 和/或二甲双胍的联合与人类胰腺导管腺癌细胞系 SUIT-2 和 MIAPaCa-2 中细胞增殖的抑制呈相加性相互作用，具有不同的吉西他滨耐药性，并且凋亡评估表明药物联合增加了这两个细胞系中的凋亡指数。吉西他滨处理诱导了两种细胞系中生存素和 XIAP 的表达，表明诱导了化疗耐药性。总之，这些数据表明，吉西他滨与 R1507 和/或二甲双胍的联合在对吉西他滨敏感性不同的胰腺癌细胞系中具有相加作用；然而，吉西他滨可能诱导化疗耐药性。
