Metformin inhibits the growth of human pancreatic cancer xenografts.
Metformin inhibits the growth of human pancreatic cancer xenografts.
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DOI：
10.1097/mpa.0b013e31827aec40
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发表时间：
2013-07
期刊：
影响因子：
2.9
通讯作者：
Rozengurt E
中科院分区：
文献类型：
--
作者：
Kisfalvi K;Moro A;Sinnett-Smith J;Eibl G;Rozengurt E
胰腺导管腺癌（PDAC）是一种毁灭性疾病，总体 5 年生存率仅为 3-5%。由于目前的疗法提供的生存益处非常有限，因此迫切需要新的治疗策略来治疗这种疾病。在这里，我们确定二甲双胍给药是否会抑制体内 PANC-1 和 MiaPaCa-2 肿瘤异种移植物的生长。使用不同的异种移植模型（包括原位植入）来确定腹膜内或口服二甲双胍是否能抑制体内胰腺癌的生长。我们证明，每天一次以不同剂量（50-250 mg/kg）腹腔给予裸鼠二甲双胍以剂量依赖性方式抑制PANC-1异种移植物的生长。二甲双胍在 50 mg/Kg 时获得显着效果，在 200 mg/Kg 时获得最大效果。二甲双胍给药还导致这些异种移植物中核糖体S6蛋白和ERK的磷酸化显着降低。在肿瘤植入之前或之后口服（2.5 mg/ml）二甲双胍还可以抑制胰腺癌异种移植物的生长。重要的是，口服二甲双胍还抑制原位异种移植的 MiaPaCa-2 肿瘤的生长。这里提出的研究提供了进一步的证据，表明二甲双胍为 PDAC 的预防和治疗提供了一种潜在的新方法。
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease, with overall 5-year survival rate of only 3-5%. As the current therapies offer very limited survival benefits, novel therapeutic strategies are urgently required to treat this disease. Here, we determined whether metformin administration inhibits the growth of PANC-1 and MiaPaCa-2 tumor xenografts in vivo. Different xenograft models, including orthotopic implantation, were used to determine whether intraperitoneal or oral administration of metformin inhibits the growth of pancreatic cancer in vivo. We demonstrate that metformin given once daily intraperitoneally at various doses (50-250 mg/kg) to nude mice inhibited the growth of PANC-1 xenografts in a dose-dependent manner. A significant effect of metformin was obtained at 50 mg/Kg and maximal effect at 200 mg/Kg. Metformin administration also caused a significant reduction in the phosphorylation of ribosomal S6 protein and ERK in these xenografts. Metformin also inhibited the growth of pancreatic cancer xenografts when administered orally (2.5 mg/ml) either prior or after tumor implantation. Importantly, oral administration of metformin also inhibited the growth of MiaPaCa-2 tumors xenografted orthotopically. The studies presented here provide further evidence indicating that metformin offers a potential novel approach for PDAC prevention and therapy.