吴晓静, 庞 雁, 庹培昱, 刘 江, 牛瑞芳, 常克力. 导向逆转剂Ab-IL2体外偶联以及协同抑瘤作用的研究[J]. 中国肿瘤临床, 2011, 38(20): 1251-1253. DOI: 10.3969/j.issn.1000-8179.2011.20.004
引用本文: 吴晓静, 庞 雁, 庹培昱, 刘 江, 牛瑞芳, 常克力. 导向逆转剂Ab-IL2体外偶联以及协同抑瘤作用的研究[J]. 中国肿瘤临床, 2011, 38(20): 1251-1253. DOI: 10.3969/j.issn.1000-8179.2011.20.004
Xiaojing WU, Yan PANG, Peiyu TUO, Jiang LIU, Ruifang NIU, Keli CHANG. The In Vivo Synergy Anti-tumor Effect of ADM and In Vivo Coupled Ab-IL2[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2011, 38(20): 1251-1253. DOI: 10.3969/j.issn.1000-8179.2011.20.004
Citation: Xiaojing WU, Yan PANG, Peiyu TUO, Jiang LIU, Ruifang NIU, Keli CHANG. The In Vivo Synergy Anti-tumor Effect of ADM and In Vivo Coupled Ab-IL2[J]. CHINESE JOURNAL OF CLINICAL ONCOLOGY, 2011, 38(20): 1251-1253. DOI: 10.3969/j.issn.1000-8179.2011.20.004

导向逆转剂Ab-IL2体外偶联以及协同抑瘤作用的研究

The In Vivo Synergy Anti-tumor Effect of ADM and In Vivo Coupled Ab-IL2

  • 摘要: 探讨利用乳腺癌单克隆抗体作为导向载体,将逆转剂IL2特异性地导向肿瘤细胞,使其发挥逆转作用的临床应用价值,为将此方法用于肿瘤的临床治疗提供医学依据。方法:分别制备人基因重组白细胞介素2(IL-2)以及人乳腺癌单克隆抗体(记为Ab),将其经过体外的偶联与纯化,并对偶联产物进行严格的质量检测,最终得到导向多药耐药(MDR)逆转剂Ab-IL2,并通过体外MDR逆转作用检测其活性保留。将对阿霉素(ADM)耐药的人乳腺癌细胞系MCF-7/ADM,种植于BALB/c裸鼠皮下,每只小鼠注射量为106个细胞,将得到的荷瘤小鼠分为三组,并于接种后的第14,19天分别进行如下处理:1)对照组:腹腔注射生理盐水;2)ADM组:腹腔注射阿霉素(1 mg/kg体重);3)协同用药组:同时注射阿霉素(1 mg/kg体重)和前述实验获得的多药耐药逆转剂Ab-IL2(1 mg/kg体重)。分别于14、16、18、20天测量肿瘤大小,并于第20天处死小鼠,取出瘤块并称重,据此计算肿瘤抑瘤率。结果:Ab-IL2的质量合格,活性保留为90.7%。多药耐药逆转剂Ab-IL2与阿霉素联合应用显示出体内协同抑瘤作用,至第20天处死小鼠时,协同用药组的抑瘤率为60.48%,是ADM组(抑瘤率19.44%)的3.11倍。结论:将单克隆抗体介导技术应用于肿瘤MDR导向逆转,可以促进逆转剂有效地发挥其应有的作用,本研究为实现临床上MDR逆转剂的成功应用提供了有力保证。

     

    Abstract: To investigate the multi-drug resistance reversal effect of IL-2 using monoclonal antibodies against breast cancer on the human breast cancer cell line MCF-7/ADM and to evaluate the feasibility of the method as an anti-tumor treatment. Methods: Recombinant human interleukin-2 and monoclonal antibodies against human breast cancer were prepared. The antibodies and cytokine were coupled, and the product, designated as Ab-IL2, was purified and its ability to reverse clinical multidrug resistance ( MDR ) was verified. Meanwhile, the retention of Ab-IL2 was measured through an in vivo MDR reversal trial. Adriamycin ( ADM )-resistant human breast cancer MCF-7 ( MCF-7/ADM ) cells were subcutaneously injected into female BALB/c nude mice at 106 cells per mouse. These mice were then divided into three groups: a. Control group, injected with normal saline; b. ADM group, injected with ADM at 1 mg/kg body weight; c. Collaborative treatment group, treated with both ADM at 1 mg/kg body weight and Ab-IL2 at 1 mg/kg body weight. The injections were given on the 14th and 19th day after inoculation. The diameter of the tumors were measured on the 14th, 16th, 18th and 20th day, and the volumes of the tumors were calculated according to the formula V = 0.5ab2. The mice were sacrificed after the last measurement, the tumor masses were surgically isolated and weighted, and the values were used to calculate the inhibition rate. Results: Ab-IL2 has a retention rate of 90.7%. Ab-IL2 showed strong synergistic antitumor effect with ADM in vivo, as suggested by the 3.11-fold higher tumor inhibition rate of the collaborative treatment group ( 60.48% ) compared with that of the ADM group ( 19.44% ) based on the data collected on the 20th day. Conclusion: Monoclonal antibodies can increase the specificity of the reversal agent, which could be helpful in reversing MDR. This study provides a safe and effective method for reversing multidrug resistance in tumors.

     

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