Liu Ya-Ping, Wu Yan-Li, Zhang Xiao-Yan, Hu Guo-Fu, Wu Yun-Xia
School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Molecular Oncology Research Institute, Tufts Medical Center, Boston, 02111, USA.
J Huazhong Univ Sci Technolog Med Sci. 2016 Feb;36(1):82-87. doi: 10.1007/s11596-016-1546-2. Epub 2016 Feb 3.
Neamine, a non-toxic derivative of neomycin, has recently been shown to have antitumor activities in various types of cancers. However, its effect on pancreatic cancer is still unknown. The study aimed to investigate its antitumor activity on pancreatic cancer and the underlying mechanisms. MTT assay was used to observe the effect of neamine on angiogenin (ANG)-induced AsPC-1 cell proliferation. Tissue microassay and immunofluorescence staining were used to detect the expression of ANG and its nuclear translocation, respectively. Tumor xenografts were established by subcutaneous inoculation of AsPC-1 pancreatic cancer cells into the right flanks of nude mice, and neamine was injected subcutaneously. Immunohistochemistry was done to observe the expression of ANG, CD31 and Ki-67 in tumor xenografts. It was found that neamine blocked the nuclear translocation of ANG effectively and inhibited ANG-induced AsPC-1 cell proliferation in a dose-dependent manner. Neamine had anti-tumor effects on AsPC-1 xenograft models. Consistently, neamine reduced the expression levels of ANG, Ki-67 and CD31 in tumor xenografts. It was concluded that neamine may be a promising agent for treatment of pancreatic cancer.
新霉素胺是新霉素的一种无毒衍生物，最近已被证明在各种类型的癌症中具有抗肿瘤活性。然而，其对胰腺癌的影响仍不清楚。该研究旨在探讨其对胰腺癌的抗肿瘤活性及其潜在机制。采用MTT法观察新霉素胺对血管生成素（ANG）诱导的AsPC-1细胞增殖的影响。分别采用组织微阵列和免疫荧光染色检测ANG的表达及其核转位。通过将AsPC-1胰腺癌细胞皮下接种到裸鼠右腹侧建立肿瘤异种移植模型，并皮下注射新霉素胺。采用免疫组织化学法观察肿瘤异种移植中ANG、CD31和Ki-67的表达。发现新霉素胺能有效阻断ANG的核转位，并以剂量依赖性方式抑制ANG诱导的AsPC-1细胞增殖。新霉素胺对AsPC-1异种移植模型具有抗肿瘤作用。一致地，新霉素胺降低了肿瘤异种移植中ANG、Ki-67和CD31的表达水平。得出的结论是，新霉素胺可能是一种有前途的胰腺癌治疗药物。
