摘要
目的:考察小分子靶向肽(RGD)_2C与力达霉素的偶联物的抗肿瘤作用。方法:MTT法观察偶联物和力达霉素在体外对人口腔鳞癌KB细胞、人乳腺癌MCF-7细胞以及人肝癌Bel 7402细胞的细胞毒性。克隆形成法观察其对人肝癌Bel 7402细胞克隆形成的抑制作用。采用C57BL/6小鼠Lewis肺癌移植瘤模型观察其实验治疗作用。结果:MTT法结果表明,偶联物对人口腔鳞癌KB细胞、人肝癌Bel 7402细胞和人乳腺癌MCF-7细胞的细胞毒性比力达霉素分别下降13倍、46倍和186倍。克隆形成法表明,偶联物对人肝癌Bel 7402细胞的克隆形成抑制率比力达霉素下降10倍。0.2,0.1,0.05 mg·kg^(-1)偶联物对C57BL/6小鼠Lewis癌皮下原发瘤的生长抑制率分别为35.8%,25.6%和10.3%;0.05 mg·kg^(-1)力达霉素对肿瘤生长的抑制率为32.4%。0.2,0.1,0.05 mg·kg^(-1)偶联物对小鼠Lewis癌肺转移的抑制率分别为69.6%,50.5%和34.2%,0.05 mg·kg^(-1)力达霉素、0.05 mg·kg^(-1)力达霉素+1 mg·kg^(-1)(RGD)_2C肽的抑制率分别为53.3%和54.9%。结论:按等细胞毒性剂量来计算,偶联物体内抗肿瘤活性和抗肿瘤转移活性比力达霉素强,提示小分子靶向肽RGD与力达霉素偶联后发挥了一定的导向作用。
Objective： To investigate the anti-tumor activity of （RGD）2C-LDM conjugate. Method： MTT assay and Clonogenie assay were used to test its cytotoxicity. Therapeutic experiment was carried out in model of subcutaneously transplanted Lewis lung carci- noma in C57BL/6 mice. Result： Determined by MTT assay, Cytotoxic activity of LDM-（RGD） 2C conjugate to human carcinoma KB cells ,human hepatoma Bel 7402 cells and human breast carcinoma MCF-7 cells is lowered 13 times ,46 times and 186 times than that of LDM. Clonogenic assay showed that Cytotoxic activity of LDM-（RGD） 2 C conjugate to human hepatoma Bel 7402 cells is lowered 10 times than that of LDM. LDM- （RGD） 2 C conjugate at doses of O. 2,0. 1 and 0.05 mg- kg- 1 inhibited the growth of subcutaneous prima- ry tumor of Lewis lung carcinoma by 35. 8% ,25.6% and 10. 3%, respectively, whereas LDM at the dose of 0.05 mg. kg-1 inhibited by 32.4%. LDM- （RGD） 2 C conjugate at above three dosages inhibited the number of pulmonary metastatic foci of Lewis lung carcinoma by 69. 6% ,50. 5% and 34. 2% ,respectively,whereas LDM at the dose of 0. 05 mg-kg-1 inhibited by 53.5% and in combination with （RGD） 2 C at the dose 1 mg. kg- 1 inhibited by 54. 9%. Conclusion： According to dosage of equivalent cytoxicity, anti-tumor activity of conjugate may be stronger than that of LDM,which indicates that （RGD）2C may display target action.
出处
《中国药师》
CAS
2010年第4期456-458,共3页
China Pharmacist
