抗hnRNPB1单克隆抗体结合^131I对肺癌小鼠靶向治疗的实验研究

Experimental study of targeting therapy of lung carcinoma in mice with ^131 I combined hnRNP B1 monoclonal antibody

目的 观察^131I-抗hnRNP B1MAb、抗hnRNP B1MAb对肺癌小鼠移植瘤的靶向治疗作用。方法 用常规氯胺-T法合成^131I-抗hnRNP B1MAb,皮下接种肺癌细胞7d后,将肺癌小鼠随机分成5组,每组6只。分别经尾静脉注射,Ⅰ组：^131I-抗hnRNP B1MAb11.1MBq/只单次治疗,Ⅱ组：^131I-抗hnRNP B1MAb2×11.1MBq/只强化治疗,Ⅲ组：Na^131I11.1MBq/只,Ⅳ组：抗hnRNP B1MAb50μg/只,Ⅴ组：生理盐水0.12ml作为对照组。干预后每周测量一次小鼠肿瘤的长径及短径,4周后处死小鼠,分离肿瘤并称其质量,计算抑瘤率,肿瘤组织做苏木素伊红（HE）染色检查。结果 治疗结束时,Ⅰ、Ⅱ、Ⅲ、Ⅳ、Ⅴ组小鼠肿瘤的平均体积分别为（3869±192）mm^3、（1987±149）mm^3、（6922±532）mm^3、（6962±509）mm^3、（6957±521）mm^3,其中I组、Ⅱ组与Ⅴ组肿瘤平均体积相比差异具有统计学意义（P〈0.05）,而I组、Ⅲ组治疗结束时肿瘤平均体积与Ⅴ组相比较无统计学意义（P〉0.05）。治疗结束时各组小鼠平均体质量差异无统计学意义（P〉0.05）。Ⅰ组强化组及Ⅱ组的抑瘤率分别为69.88%和41.35%。各治疗组小鼠未发现明显的不良反应。结论 抗hnRNP B1MAb结合^131I对小鼠肺癌的生长具有显著抑制作用,抑制作用呈量效关系,未发现明显的毒副作用。单纯抗hnRNP B1MAb及Na^131I未出现明显抑制肿瘤生长的作用。

Objective To evaluate the targeted therapeutic efficiency of ^131I-anti hnRNP B1 MAb and anti hnRNPB1 MAb on the mice with implanted Lewis lung carcinoma. Methods Anti hnRNP B1 MAb was combined with ^131I by routine chloramines-T method. Lewis lung cancer tumor cells were injected by subcutaneous inoculation. After 7 d,the mice were divided into five groups, including ^131 I-anti hnRNP B1 MAb（11. 1 MBq per mouse） single dose,^131 I-anti hnRNP B1 MAb（ll. 1 MBq per mouse） double dose,Na^131 I alone（11. 1 MBq per mouse） ,anti-hnRNP B1 MAb alone（50 μg per mouse） ,and control group. Each drug was injected by the tail vein of the mouse respectively. The toxic response was observed every day and the size of the tumor was measured weekly and the mice were killed four weeks after treatment. The tumor was resected and weighed. The inhabited ratio of tumor growth was calculated and tumor tissues were detected by HE staining. Results After treatment the average volume of the tumor in each group was （3869±192） mm^3 , （1987±149） mm^3 , （6922 ± 532） mm^3 , （6962± 509） mm^3 , （6957 ± 521） mm^3 respectively with ^131I- hnRNP B1 MAb single dose,^131 I-hnRNP B1 MAb double doses,^131 I alone, hnRNP B1 MAb alone, and control group. The average volumes of the tumors of the ^131 I-hnRNP B1 MAb single dose and ^131 I-hnRNP B1 MAb double dose（interval 3 days） were significantly less than that of the control group （ P 〈 0.05）. The average volume of the tumors showed no significant different in groups（ P 〉0.05）. The growth of implanted tumor was inhibited by 69.88 % and 41.35% at groups treated with ^131 I-hnRNP B1 MAb double dose and ^131 I-hnRNP B1 MAb single dose respectively. Na^131 I and anti hnRNP B1 MAb group did not show difference in tumor volume and weight compared to the control group. Little obvious side effect was found. Conclusions Anti hnRNPB1 MAb combined with ,^131I can inhibit the tumor growth of transplantation tumor on mice and has dose-response relationship. Little side effects in therapeutic were found. Anti hnRNPB1 MAb and Na^131 I have not shown the inhibition of the tumor growth.