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★

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，IC₅₀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G₂/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。

Abstract:

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 IC₅₀ 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 G₂/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.