化学合成DFV-紫杉烷类化合物对未分化甲状腺癌细胞的抗肿瘤作用研究  

Antitumor effects of chemically synthesized DFV-taxane compounds on anaplastic thyroid cancer cells

作　　者：王美晨 王昌伟 冯超 Iwao Ojima WANG Meichen;WANG Changwei;FENG Chao;OJIMA Iwao(Department of Medical Oncology,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an,710061,Shaanxi,China;International Joint Research Center for Tumor Precision Medicine of Shaanxi Province,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an,710061,Shaanxi,China;Department of Internal Medicine,University of Michigan,Ann Arbor,48109-5368,MI,USA;Institute of Chemical Biology and Drug Discovery,Stony Brook University,the State University of New York,New York,11794-3400,NY,USA)

机构地区：[1]西安交通大学第一附属医院肿瘤内科,陕西西安710061 [2]西安交通大学第一附属医院陕西省肿瘤精准医学重点实验室,陕西西安710061 [3]密歇根大学医学院,美国密歇根州安娜堡48109-5368 [4]纽约州立大学石溪分校化学生物与药物研究所,美国纽约州纽约11749-3400

出　　处：《肿瘤药学》2024年第2期179-185,共7页Anti-Tumor Pharmacy

基　　金：西安交通大学第一附属医院基金(2022QN-27);西安交通大学第一附属医院优秀青年医学人才培养计划。

摘　　要：目的探索化学合成DFV-紫杉烷类化合物对未分化甲状腺癌细胞的抗肿瘤作用及可能机制。方法噻唑蓝(MTT)实验测定DFV-紫杉烷类化合物对肿瘤细胞增殖及细胞活性的影响;紫外分光光度计测定新型紫杉烷类化合物处理后肿瘤细胞的存活情况;克隆形成实验评价新型紫杉烷类化合物对肿瘤细胞增殖能力的敏感性;结晶紫染色计数存活克隆数;流式细胞仪检测新型紫杉烷类化合物对肿瘤细胞周期分布的影响。结果甲状腺癌细胞系8505C和8305C经四种不同的DFV-紫杉烷类化合物处理后,IC_(50)在0.5~5.5 nmol·L^(-1)之间;不同药物处理后,甲状腺癌细胞的增殖能力显著降低(P<0.001);不同浓度的DFV-紫杉烷类化合物可不同程度地抑制甲状腺癌细胞的克隆形成能力(P<0.001);DFV-紫杉烷类化合物可诱导甲状腺癌细胞G_(2)/M期周期阻滞(P<0.001),从而抑制甲状腺癌细胞的生长。结论四种化学合成DFV-紫杉烷类化合物对未分化甲状腺癌细胞具有生长抑制和抗肿瘤作用。Objective To explore the anti-tumor effects and possible mechanisms of chemically synthesized DFV-taxane compounds on anaplastic thyroid cancer cells.Methods MTT assays were performed to determine the impact of the DFV-taxane compounds on tumor cell proliferation and viability.UV spectrophotometry was used to assess cell survival after treatment with the DFV-taxane compounds.Clone formation assays were conducted to evaluate the effect of DFV-taxane compounds on the proliferation ability of tumor cells.Crystal violet staining was employed to count surviving clones.Flow cytometry was utilized to detect the effects of the novel taxanes on the cell cycle distribution of tumor cells.Results After treatment with four different DFV-taxane compounds,the IC_(50) values for anaplastic thyroid cancer cell lines 8505C and 8305C ranged between 0.5~5.5 nmol·L^(-1).The proliferation ability of thyroid cancer cells was significantly reduced after treatment with different DFV-taxane compounds(P<0.001).Different concentrations of DFV-taxane compounds inhibited the clone formation ability of thyroid cancer cells to varying degrees(P<0.001).The DFV-taxane compounds induced G_(2)/M phase cell cycle arrest(P<0.001),thereby exerting growth-inhibitory effects on thyroid cancer cells.Conclusion Four chemically synthesized DFV-taxane compounds exhibit growth inhibition and antitumor effects on anaplastic thyroid cancer cells.

关 键 词：DFV-紫杉烷类化合物 未分化甲状腺癌 抗肿瘤作用 

分 类 号：R736.1[医药卫生—肿瘤]