噻吩-N-4甲基缩氨基硫脲及其银离子配合物对EC109增殖和凋亡影响

Effects of thiophene-2-carboxaldehyde N(4)-methylthiosemicarbazone and its Ag(Ⅰ)complex on proliferation and apoptosis of EC109

目的用食管癌细胞EC109体外鉴定噻吩-N-4甲基缩氨基硫脲(N)及其过渡金属配合物噻吩-N-4甲基缩氨基硫脲银(N-Ag)的抗肿瘤生物活性,探讨其可能机制。方法采用四甲基偶氮唑法(MTT法)测定上述两种药物体外对食道癌细胞EC109生长抑制率;采用吖啶橙荧光染色和吉姆萨染色观察药物对食道癌细胞EC109形态影响;采用流式细胞仪检测细胞周期的改变和细胞的凋亡情况。结果 N-Ag对食道癌EC109的增殖有较强的抑制作用,且成量效和时效关系;实验组能观察到细胞凋亡形态;流式细胞仪检测结果表明在低剂量N-Ag作用下食道癌细胞EC109部分凋亡,且随着剂量增大,凋亡量增加,细胞周期被阻滞在G0/G1。结论对于食道癌细胞EC109配体N无抗肿瘤活性,络合了Ag+后使N-Ag有明显的抗肿瘤活性,其作用机制可能是通过作用于细胞周期从而诱发细胞凋亡的。

Aim To study the anti-tumor activity and the possible mechanism of thiophene-2-carboxaldehydeN（4）-methylthiosemicarbazone and its Ag（Ⅰ） complex for esophageal EC109 in vitro.Methods The effect of the thiophene-2-carboxaldehydeN（4）-methyl thiosemicarbazone and its Ag（Ⅰ） complex on cell proliferation for esophageal EC109 in vitro was tested by MTT method.Giemsa staining and acridine orange（AO） fluorescence staining were used to observe the morphological changes of the esophageal EC109.Cell apoptosis and cell cycle distribution were detected by flow cytometry.Results The results indicated its Ag（Ⅰ） complex had strong inhibitory effect on EC109 cell proliferation in a dose-and-time dependent manner;Typical morphological changes of apoptosis were also observed in the esophageal EC109.The result of flow cytometry showed the Ag（Ⅰ） complex led to cell apoptosis partly in lower concentrations,and the apoptosis increased in a concentration dependent manner,and inhibited G0/G1 phase from entering S phase.Conclusions The ligand N has no anti-tumor effect at all on esophageal EC109,but the Ag（Ⅰ）complex N-Ag exhibits significant anti-tumor activity after introducing Ag ion,and possibly induces cell apoptosis by blocking cell cycle.