Huai Yanyan, Zhang Yushan, Xiong Xunhao, Das Shamik, Bhattacharya Resham, Mukherjee Priyabrata
Department of Pathology, the University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Peggy and Charles Stephenson Cancer Center, the University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Cell Stress. 2019 Jul 31;3(8):267-279. doi: 10.15698/cst2019.08.195.
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid cancers with dismal prognosis. Several mechanisms that are mainly responsible for aggressiveness and therapy resistance of PDAC cells include epithelial to mesenchymal transition (EMT), stemness and Mitogen Activated Protein Kinase (MAPK) signaling. Strategies that inhibit these mechanisms are critically important to improve therapeutic outcome in PDAC. In the current study, we wanted to investigate whether gold nanoparticles (AuNPs) could sensitize pancreatic cancer cells to the chemotherapeutic agent gemcitabine. We demonstrated that treatment with AuNPs of 20 nm diameter inhibited migration and colony forming ability of pancreatic cancer cells. Pre-treatment with AuNPs sensitized pancreatic cancer cells to gemcitabine in both viability and colony forming assays. Mechanistically, pre-treatment of pancreatic cancer cells with AuNPs decreased gemcitabine induced EMT, stemness and MAPK activation. Taken together, these findings suggest that AuNPs could be considered as a potential agent to sensitize pancreatic cancer cells to gemcitabine.
胰腺导管腺癌（PDAC）是最致命的实体癌之一，预后极差。导致PDAC细胞具有侵袭性和治疗抗性的几种主要机制包括上皮-间质转化（EMT）、干性和丝裂原活化蛋白激酶（MAPK）信号传导。抑制这些机制的策略对于改善PDAC的治疗效果至关重要。在本研究中，我们想探究金纳米颗粒（AuNPs）是否能使胰腺癌细胞对化疗药物吉西他滨敏感。我们证明，用直径为20 nm的AuNPs处理可抑制胰腺癌细胞的迁移和集落形成能力。在活力和集落形成试验中，用AuNPs预处理可使胰腺癌细胞对吉西他滨敏感。从机制上讲，用AuNPs预处理胰腺癌细胞可降低吉西他滨诱导的EMT、干性和MAPK激活。综上所述，这些发现表明AuNPs可被视为使胰腺癌细胞对吉西他滨敏感的潜在药物。
