Abstract：
Silver has been in clinical use since ancient times and silver nanoparticles (AgNPs) have attracted attention in cancer therapy. We investigated the mechanisms by which AgNPs inhibit pancreatic ductal adenocarcinoma (PDAC). AgNPs were synthesized and 3 human PDAC and 2 nonmalignant primary cell lines were treated with AgNPs. MTT, MAPK, colony, spheroid and scratch assays, Western blotting, TEM, annexin V, 7-AAD, and H2DCFDA staining, FACS analysis, mRNA array and bioinformatics analyses, tumor xenograft transplantation, and immunohistochemistry of the treated cells were performed. We found that minimal AgNPs amounts selectively eradicated PDAC cells within a few hours. AgNPs inhibited cell migration and spheroid and colony formation, damaged mitochondria, and induced paraptosis-like cell death with the presence of cytoplasmic vacuoles, dilation of the ER and mitochondria, ROS formation, MAPK activity, and p62 and LC3b expression, whereas effects on the nucleus, DNA fragmentation, or caspases were not detectable. AgNPs strongly decreased tumor xenograft growth without side effects and reduced the expression of markers for proliferation and DNA repair, but upregulated paraptosis markers. The results highlight nanosilver as complementary agent to improve the therapeutic efficacy in pancreatic cancer.
摘要：
银自古以来就在临床上使用，银纳米颗粒（AgNPs）在癌症治疗中引起了人们的关注。我们研究了AgNPs抑制胰腺导管腺癌（PDAC）的机制。合成AgNP并用AgNP处理3个人PDAC和2个非恶性原代细胞系。MTT,MAPK,殖民地,球体和划痕分析，西方印迹,TEM,附件五，7-AAD,和H2DCFDA染色，FACS分析,mRNA阵列和生物信息学分析，肿瘤异种移植,并对处理过的细胞进行免疫组织化学。我们发现在数小时内选择性根除PDAC细胞的AgNPs量最少。AgNPs抑制细胞迁移和球体和集落形成，受损的线粒体，并在细胞质液泡存在的情况下诱导凋亡样细胞死亡，内质网和线粒体的扩张，ROS形成,MAPK活动，p62和LC3b表达，而对细胞核的影响，DNA片段化,或胱天蛋白酶检测不到。AgNPs显著降低肿瘤移植瘤生长，无副作用，降低增殖和DNA修复标志物的表达，但上调了上倾标记。结果强调了纳米银作为改善胰腺癌治疗效果的补充剂。
