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作 者:曹萍[1] 陈知航[1] 车津晶[1] 单成启[1] 刘运龙[1] 程远国[1]
机构地区:[1]军事医学科学院微生物流行病研究所,北京100071
出 处:《生物技术通讯》2010年第3期363-367,405,共6页Letters in Biotechnology
摘 要:目的:比较国产重组C225与国外已上市同类药Erbitux是否具有相似或更好的与表皮生长因子受体(EGFR)的竞争结合力及体内外抗肿瘤药效。方法:构建EGFR高表达的人结肠癌HT-29细胞裸鼠移植瘤模型,观察静脉注射国产重组C225对肿瘤生长的抑制作用,并评价其对肿瘤细胞诱导细胞凋亡和增殖的抑制作用。结果:HT-29结肠癌裸鼠移植瘤模型对单独应用的国产C225或Erbitux敏感性都很差,对单独应用CPT-11的敏感性也较差,但当国产C225和CPT-11联合应用后抗肿瘤作用大大提高,2次实验的相对肿瘤增殖率T/C(%)分别为20.0%(P<0.05)和19.0%(P<0.05)。对人结肠癌HT-29细胞抑制增殖和诱导凋亡作用的影响研究结果显示,国产C225与CPT-11联合疗法的凋亡指数/增生指数比,是单独使用国产C225或单独使用CPT-11的4.3倍以上。结论:在人结肠癌HT-29裸鼠移植瘤模型中联合应用国产C225和CPT-11可以抑制EGFR,对肿瘤细胞有很好的诱导凋亡作用和抑制增殖作用,这种联合疗法对于CPT-11耐受的结直肠癌具有很好疗效。Objective:Compare domestic recombination C225 with marketed product Erbitux,in order to evaluate whether it has similar or better ability of affinity with epidermal growth factor receptor(EGFR) competitively,and effect of anti-tumor in vivo or vitro.Methods:The model of human colon cancer cell line HT-29 in nude mice was established.Observe the inhibiting / killing effects on tumor growth by intravenous injecting recombination C225 and assess the tumor-induced effects of apoptosis and proliferation inhibition of it.Results:The sensitivity of transplanted human colon cancer cell HT-29 nude mice model to independently used recombination C225 and Er-bitux was very bad,and independently used CPT-11 as well.However,when combine recombination C225 and CPT-11 together,the anti-tumor effect was highly increased,the two relative tumor proliferation rate T / C(%) was 20.0%(P0.05) and 19.0%(P0.05) separately.The result of researching the apoptosis / proliferation effects of human colon caner cell HT-29 showed that,if use the combination of domestic C225 and CPT-11,the index was more than 4.3 times of the one that use domestic C225 or CPT-11 independently.Conclusion:The use of domestic C225 and CPT-11 in nude mice HT-29 xenograft model could inhibit the functions of EGFR.Domestic C225 in combination with CPT-11 had very good inducing effect to tumor cell apoptosis and inhibit the proliferation of tu-mor cell well.
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