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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 antitumor effect of a conjugate of small molecule targeting peptide (RGD) _2C and lidamycin. Methods: The cytotoxicity of conjugate and lidamycin on human oral squamous cell carcinoma KB cells, human breast cancer MCF-7 cells and human hepatocellular carcinoma Bel 7402 cells were observed by MTT assay. Clone formation method was used to observe the inhibitory effect on the colony formation of human hepatoma Bel 7402 cells. C57BL / 6 mouse Lewis lung cancer xenograft model was used to observe the experimental therapeutic effect. Results: MTT assay showed that the cytotoxicity of the conjugates to human KB cells, human hepatocellular carcinoma Bel 7402 cells and human breast cancer MCF-7 cells were 13 times, 46 times and 186 times lower than that of doxycycline. Clone formation assay showed that the inhibition of clonogenicity of conjugate on human hepatoma Bel 7402 cells was 10-fold lower than that of doxycycline. The inhibitory rates of 0.2,0.1,0.05 mg · kg -1 conjugate on the subcutaneous tumor growth of Lewis lung carcinoma in C57BL / 6 mice were 35.8%, 25.6% and 10.3%, respectively; 0.05 mg · kg -1, 1) The inhibitory rate of lidamycin on tumor growth was 32.4%. The inhibitory rates of the conjugates with 0.2, 0.1 and 0.05 mg · kg -1 were 69.6%, 50.5% and 34.2%, respectively, and 0.05 mg · kg -1 0.05 mg · kg -1 lentiomycin +1 mg · kg -1 RGD -2C peptide were 53.3% and 54.9%, respectively. Conclusions: The antitumor activity and antitumor activity of the conjugate were stronger than that of doxycycline in terms of isocytotoxic doses, suggesting that the RGD-targeting peptide binds to lidamycin to some extent .