Department of Hepatobiliary-Pancreatic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, P.R. China.
Int J Oncol. 2012 Jun;40(6):1849-57. doi: 10.3892/ijo.2012.1389. Epub 2012 Feb 29.
Pancreatic cancer is a highly aggressive malignant disease. Gemcitabine is currently the standard first-line chemotherapeutic agent for pancreatic cancer. As members of apoptosis inhibitors, Survivin and XIAP play an important role in chemotherapy resistance in pancreatic cancer. Emodin has therapeutic potential against cancers. This study was designed to investigate whether combination therapy with gemcitabine and emodin enhanced antitumor efficacy in pancreatic cancer. The application of the combination therapy triggered significantly higher frequency of pancreatic cancer cell apoptosis. Our research demonstrated that the combination of emodin and gemcitabine resulted in significantly reduced tumor volumes compared to gemcitabine or emodin treatment alone. Immunohistochemistry and western immunoblot analyses showed that Survivin and XIAP expression were downregulated in emodin and the combination groups compared to the other two groups. Reverse transcriptase polymerase chain reaction analyses showed that Survivin and XIAP mRNA expression in emodin and the combination groups were downregulated significantly compared to the other two groups. Furthermore, the expression of the nuclear transcription factor κB (NF-κB) protein and NF-κB mRNA were downregulated in the emodin and the combination groups. DNA-binding activity of NF-κB was inhibited in emodin and combination groups compared to the other groups. This study suggests that emodin potentiates the antitumor effects of gemcitabine in PANC-1 cell xenografts via promotion of apoptosis and IAP suppression.
胰腺癌是一种高度侵袭性的恶性疾病。吉西他滨是目前治疗胰腺癌的标准一线化疗药物。Survivin 和 XIAP 作为凋亡抑制剂的成员，在胰腺癌的化疗耐药中发挥重要作用。大黄素具有治疗癌症的潜力。本研究旨在探讨吉西他滨联合大黄素治疗是否能增强胰腺癌的抗肿瘤疗效。联合治疗的应用显著增加了胰腺癌细胞凋亡的频率。我们的研究表明，与吉西他滨或大黄素单药治疗相比，大黄素和吉西他滨联合治疗显著降低了肿瘤体积。免疫组化和 Western 免疫印迹分析显示，与其他两组相比，大黄素和联合组中 Survivin 和 XIAP 的表达下调。逆转录聚合酶链反应分析显示，与其他两组相比，大黄素和联合组中 Survivin 和 XIAP 的 mRNA 表达明显下调。此外，大黄素和联合组的核转录因子 κB（NF-κB）蛋白和 NF-κB mRNA 的表达下调。与其他组相比，大黄素和联合组中 NF-κB 的 DNA 结合活性受到抑制。本研究表明，大黄素通过促进凋亡和抑制 IAP 增强了吉西他滨在 PANC-1 细胞异种移植中的抗肿瘤作用。
