摘要
目的设计合成两种不同结构的平面正方形铂(II)配合物,探讨其抗肿瘤活性及机制。方法通过噻唑蓝(MTT)法对配合物4和配合物5的体外细胞毒性进行测试;利用ICP-MS(Inductively coupled plasma mass spectrometry)方法对配合物在细胞内分布进行分析;通过蛋白免疫印迹的方法检测配合物影响肿瘤细胞核内γH2AX抗体的变化;使用Caspase-Glo®试剂盒检测配合物损伤细胞的形式,并且通过扫描电镜拍摄观察细胞损伤的形式。结果配合物4和配合物5的细胞半数抑制浓度(IC_(50))值均明显低于顺铂,在HeLa细胞中分别为(4.4±0.2)和(8.2±0.2)μmol·L^(-1),配合物4细胞毒性是顺铂的约4倍。配合物4和配合物5能定位在细胞核内,以细胞凋亡方式损伤细胞核DNA,具有较强的体外抗肿瘤活性。结论氮杂环卡宾铂(II)配合物具有良好的细胞毒性,通过诱导DNA损伤杀伤肿瘤细胞。
Objective To design and synthesize two planar square platinum(Ⅱ) complexes with different structures, and to explore their anti-tumor activity and mechanism. Methods The in vitro cytotoxicity of complex 4 and 5 were tested by thiazole blue(MTT) method;the intracellular distribution of complexes was analyzed by inductively coupled plasma mass spectrometry(ICP-MS) method;The protein immunoblotting method was used to detect the effect of the complex on the changes of the γH2 AX antibody in the tumor cell nucleus;The Caspase-Glo® kit was used to detect the form of damaged cells through scanning electron microscopy for the designed and synthesized complex. Results The experimental results show that the IC50 values of the two platinum(Ⅱ) complexes designed and synthesized in this paper were significantly lower than those of cisplatin in Hela cells with the values of(4.4±0.2) μmol·L^(-1) vs(8.2±0.2) μmol·L^(-1). It means the cytotoxicity of complex 4 was about 4 times higher than that of cisplatin;Complex 4 and Complex 5 could be located in the cell nucleus, and cause damage in the nuclear DNA leading to the apoptosis. Both complexes have strong anti-tumor activity in vitro. Conclusion The azacyclocarbene platinum(Ⅱ) complex has good cytotoxicity and kills tumor cells by inducing DNA damage.
作者
梁冰冰
唐成飞
何娟
姚华刚
LIANG Bingbing;TANG Chengfei;HE Juan;YAO Huagang(School of Medicine and Chemical Engineering,Zhongshan Campus,Guangdong Pharmaceutical University,Zhongshan 528400,China)
出处
《医药导报》
CAS
北大核心
2021年第6期740-744,共5页
Herald of Medicine
关键词
金属铂配合物
氮杂环卡宾铂
抗肿瘤活性
Metal platinum complex
Azacyclocarbene platinum
Antitumor activity
