Kim Nayoung, Lee Sang Hyub, Son Jun Hyuk, Lee Jae Min, Kang Min-Jung, Kim Bo Hye, Lee Jung-Su, Ryu Ji Kon, Kim Yong-Tae
Department of Convergence Medicine & Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Department of Internal Medicine and Liver Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea
Anticancer Res. 2016 Nov;36(11):6109-6116. doi: 10.21873/anticanres.11201.
Cholangiocarcinoma (CCA) is a malignancy with poor prognosis and limited therapeutic options. Effective prevention and treatment of CCA require developing novel anticancer agents and improved therapeutic regimens. As natural products are concidered a rich source of potential anticancer agents, we investigated the anticancer effect of fisetin in combination with gemcitabine.
Cytotoxic effect of fisetin and gemcitabine on a human CCA cell line SNU-308 was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and apoptosis assay using propidium iodine and annexin V. Molecular mechanisms of fisetin action in CCA were investigated by western blotting.
Fisetin was found to inhibit survival of CCA cells, through strongly phosphorylating ERK. It also induced cellular apoptosis additively in combination with gemcitabine. Expression of cellular proliferative markers, such as phospho-p65 and myelocytomatosis (MYC), were reduced by fisetin.
These results suggest fisetin in combination with gemcitabine as a candidate for use in improved anticancer regimens.
胆管癌（CCA）是一种预后较差且治疗选择有限的恶性肿瘤。有效预防和治疗CCA需要开发新型抗癌药物和改进治疗方案。由于天然产物被认为是潜在抗癌药物的丰富来源，我们研究了非瑟酮与吉西他滨联合使用的抗癌效果。
通过3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐试验以及使用碘化丙啶和膜联蛋白V的凋亡试验，评估非瑟酮和吉西他滨对人CCA细胞系SNU-308的细胞毒性作用。通过蛋白质印迹法研究非瑟酮在CCA中的作用分子机制。
发现非瑟酮通过强烈磷酸化细胞外信号调节激酶（ERK）来抑制CCA细胞的存活。它还与吉西他滨联合使用时可额外诱导细胞凋亡。非瑟酮可降低细胞增殖标志物如磷酸化p65和原癌基因（MYC）的表达。
这些结果表明非瑟酮与吉西他滨联合使用可作为改进抗癌方案的候选药物。
