新型铂类化合物LLC-0601与顺铂、舒铂体外对L-02、HK-2细胞的毒性比较研究  

To compare toxicity of a new platinum complax LLC-0601 with cisplatin and heptaplatin on L-02 cells and HK-2 cells in vitro

作　　者：王振宇[1] 梅茸[2] 宋京风[1] 刘伟平[3] 董瑞涛[4] 陆瑛[1] 

机构地区：[1]昆明医科大学生物医学工程研究中心,云南昆明650500 [2]云南省第一人民医院 [3]昆明贵金属研究所 [4]昆明学院医学院

出　　处：《毒理学杂志》2012年第5期350-355,共6页Journal of Toxicology

基　　金：云南省教育厅科学研究基金项目资助(09J0055;2012C211)

摘　　要：目的比较新型铂类化合物LLC-0601与舒铂、顺铂体外对人胚胎肝细胞(L-02)和人肾小管上皮细胞(HK-2)的毒性。方法采用不同浓度的LLC-0601、顺铂、舒铂分别与L-02细胞和HK-2细胞作用48 h后,四甲基偶氮唑盐(MTT)法检测并计算细胞增殖抑制率,计算IC50;取细胞培养液全自动生化分析仪检测乳酸脱氢酶(LDH)漏出量;显微镜下观察细胞形态改变。结果 LLC-0601、顺铂、舒铂作用两株细胞48 h后,同等剂量下LLC-0601对L-02细胞和HK-2细胞的抑制率都是最低,舒铂次之,顺铂最强,组间比较差异有统计学意义(P<0.05);检测两株细胞培养液中LDH含量,LLC-0601在较高剂量下才出现LDH升高,而顺铂和舒铂在较低剂量下LDH既有明显变化,组间比较差异有统计学意义(P<0.05),其中顺铂又强于舒铂(P<0.05)。3个铂类化合物细胞形态改变均表现随给药浓度增加,出现细胞核空泡样改变,细胞膜不完整,继续增加给药浓度后细胞死亡。结论 LLC-0601体外对L-02和HK-2细胞的毒性明显低于顺铂、舒铂,是一个有开发前景的新化合物。Objective To compare toxicity of a new platinum complax LLC-0601 with Cisplatin and heptaplatin on Human fetal liver cell （L-02） and human renal tubular epithelial cell （HK-2） in vitro. Methods L-02 cells and HK-2 cells were treated 48 hours with different concentrations of LLC-0601, cisplatin and heptaplatin, respectively, by MTT assays and calculated IC50. In addition, the concentrations of Lactic acid dehydrogenase （LDH） in cell culture fluid were measured by automatic biochemistry analyzer; morphological changes were observed. Results LLC-0601, cisplatin and heptaplatin treated two cells for 48 hours, at the same doses, the inhibition effect of LLC-0601 on L-02 cells and HK-2 cells were significantly lower than that of cisplatin and heptaplatin （P 〈 0. 05）. Detected LDH levels of two cell culture fluid, LLC-0601 at higher doses to appeared the change of LDH, but.cisplatin and heptaplatin at lower doses showed the increased LDH （ P 〈 0. 05 ）. Furthermore, the level of LDH in cisplatin treated was stronger than that of heptaplatin （ P 〈 0. 05 ）. Morphological changes showed that two cells by three platinum compounds treated appear vacuolar changes in the nucleus, cell membrane is not complete, and continued to increase drug concentration to cell death. Conclusion The toxicity of LLC-0601 on L-02 cell and HK-2 cell are significantly lower than that of cisplatin and heptaplatin in vitro. It is a potential compounds.

关 键 词：LLC-0601 舒铂 顺铂 毒性 

分 类 号：R994[医药卫生—毒理学] R73-3[医药卫生—药学]