Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Invest New Drugs. 2018 Feb;36(1):20-27. doi: 10.1007/s10637-017-0508-2. Epub 2017 Sep 5.
Despite great improvements in surgical procedures and chemotherapy, pancreatic cancer remains one of the most aggressive and fatal human malignancies, with a low 5-year survival rate. Therefore, novel therapeutic strategies for the prevention and treatment of pancreatic cancer are urgently needed. The present study aimed to investigate the mechanisms by which metformin exerts its anticancer effects on the microRNA-mRNA interactions in human pancreatic cancer. Microarray and systematic analyses revealed that the anti-pancreatic cancer effects of metformin were correlated with 3 up-regulated microRNAs and 4 of their target mRNAs. In addition, the microarray and systematic analyses ultimately demonstrated that 3 microRNAs regulated 4 key mRNAs in a sub-pathway of pancreatic cancer and then affected growth, angiogenesis, and apoptosis. This finding may provide a deeper understanding of the mechanisms by which metformin suppresses proliferation and angiogenesis and promotes apoptosis in pancreatic cancer cells. Collectively, this experiment improves the understanding of the mechanisms by which metformin suppresses pancreatic cancer and indicates that metformin, the most commonly used drug for the treatment of diabetes mellitus, may be a promising candidate agent for the treatment of pancreatic cancer.
尽管手术和化疗方面取得了巨大进展，但胰腺癌仍然是最具侵袭性和致命性的人类恶性肿瘤之一，其 5 年生存率很低。因此，迫切需要新的治疗策略来预防和治疗胰腺癌。本研究旨在探讨二甲双胍通过调节 microRNA-mRNA 相互作用对人胰腺癌发挥抗癌作用的机制。微阵列和系统分析表明，二甲双胍的抗胰腺癌作用与 3 个上调的 microRNA 和 4 个其靶 mRNAs 相关。此外，微阵列和系统分析最终表明，3 个 microRNAs 调节了胰腺癌亚途径中的 4 个关键 mRNAs，进而影响了生长、血管生成和细胞凋亡。这一发现可能为深入了解二甲双胍抑制胰腺癌细胞增殖、血管生成和促进凋亡的机制提供了依据。总之，该实验加深了我们对二甲双胍抑制胰腺癌的机制的理解，并表明二甲双胍作为治疗糖尿病最常用的药物，可能成为治疗胰腺癌的有前途的候选药物。
