新型卟啉化合物抗肿瘤细胞增殖作用筛选及机理

目的 研究6种新型金属卟啉化合物对肝癌细胞（HepG2）、肺癌细胞（A549）和乳腺癌细胞（MCF-7）的抗增殖作用及机理.方法 SRB和MTT法观察药物对肿瘤细胞增殖的影响;Griess法测定细胞上清液中NO自由基的含量;Giemsa染色观察细胞形态学变化;流式细胞仪检测细胞凋亡;DNA完整性检测.结果 6种化合物对肿瘤细胞生长均有抑制作用,效果较好的两种药物是Rup-03 （IC50 =2.95×10 5mol/L）和Rup-04（IC50=41.59mol/L）;随药物浓度（10-10～ 10-5mol/L）升高,细胞内NO含量随之升高,且Rup-03优于Rup-04;Giemsa染色观察Rup-03（10-9～10 6mol/L）随浓度增加凋亡细胞明显增多,且在108～10 6mol/L浓度范围,流式细胞仪检测细胞凋亡率增加,并观察到DNA发生了降解.结论 在6种新型金属卟啉化合物中,Rup-03抗HepG2细胞增殖作用最显著,其可能的作用机制与产生自由基诱导细胞凋亡有关.

Study of the effects and mechanisms of novel porphyrins on the anti-tumor cell proliferation

Objective To study the anti - tumor proliferative effects and mechanisms of six synthesized metal porphyrins on the hepatoma cells （ HepG2 ）, lung carcinoma cells （ A549 ） and breast cancer cells （ MCF - 7 ）. Methods The proliferation ratios of cancer cells were determined by the SRB and MTT assays;The contents of NO in the cell culture supernate were detected by the Griess; The ceil morphology was observed by the Giemsa staining; The apoptosis was assayed with flow cytometry and DNA integrity detection. Results All of the six porphyrins had inhibitory effects on the growth of tumor cells, Rup -03 （IC50 =2.95 × 10^-5 mol/L） and Rup -04 （IC50 =41.59mol/L） were the better. With the concentration of drugs contents of NO in cells were elevated and the effect of Rup -03 is better 10 ^- 10 - 10 ^-5 mol/L） increasing, the an the Rup- 04. The numbers of apoptotic cells were increased significantly with the increasing concentration of Rup -03 by the Giemsa staining. Within 10^-8 -10^-6moL/L, the apoptosis rates were increased and DNA had degraded. Conclusion Among six new metal porphyrin compounds, the anti - HepG2 cell proliferative effect of Rup -03 is the most obvious, and its mechanism is related to induce cell apoptosis by the production of free radicals.