封 云, 何红伟, 李保卫, 张征仙, 陈 曦, 李晓芳. 抗Ⅳ型胶原酶抗体Fab'片段力达霉素偶联物的抗肿瘤侵袭转移作用J. 药学学报, 2011,46(12): 1462-1465.
引用本文: 封 云, 何红伟, 李保卫, 张征仙, 陈 曦, 李晓芳. 抗Ⅳ型胶原酶抗体Fab'片段力达霉素偶联物的抗肿瘤侵袭转移作用J. 药学学报, 2011,46(12): 1462-1465.
FENG Yun, HE Hong-wei, LI Bao-wei, ZHANG Zheng-xian, CHEN Xi, LI Xiao-fang. Inhibitory effects of the immunoconjugate composed of anti-type IV collagenase antibody Fab' fragment and lidamycin on tumor invasion and metastasisJ. 药学学报, 2011,46(12): 1462-1465.
Citation: FENG Yun, HE Hong-wei, LI Bao-wei, ZHANG Zheng-xian, CHEN Xi, LI Xiao-fang. Inhibitory effects of the immunoconjugate composed of anti-type IV collagenase antibody Fab' fragment and lidamycin on tumor invasion and metastasisJ. 药学学报, 2011,46(12): 1462-1465.

抗Ⅳ型胶原酶抗体Fab'片段力达霉素偶联物的抗肿瘤侵袭转移作用

Inhibitory effects of the immunoconjugate composed of anti-type IV collagenase antibody Fab' fragment and lidamycin on tumor invasion and metastasis

  • 摘要:

    本研究拟阐明力达霉素 (LDM) 与抗型胶原酶单抗小型化免疫偶联物Fab'-LDM的抗肿瘤侵袭转移作用。采用Boyden小室体外侵袭实验, 检测Fab'-LDM免疫偶联物对人纤维肉瘤HT-1080细胞侵袭能力的影响; 进一步采用明胶酶谱实验研究其对MMP-2MMP-9分泌的影响, 以及RT-PCR法检测其对TIMP-1 mRNA表达水平的影响; 应用裸鼠体内移植人纤维肉瘤HT-1080模型, 探讨Fab'-LDM对肿瘤的生长抑制作用。Boyden小室体外侵袭结果表明, Fab'-LDMHT-1080侵袭转移存在剂量依赖性抑制作用: Fab'-LDM (510 nmol·L−1) 的侵袭抑制作用分别达到 (60 ± 12) % (79 ± 11) % 明胶酶谱实验证实, Fab'-LDM偶联物 (510 nmol·L−1) MMP-2MMP-9型明胶酶分泌的抑制作用达到 (42 ± 8) %(54 ± 6) % (57 ± 3) %(87 ± 1) %。同时RT-PCR检测显示, 10 nmol·L−1 Fab'-LDM显著提高TIMP-1 mRNA表达水平。体内实验显示, 与对照相比, Fab' 片段组、LDM组和Fab'-LDM组的肿瘤生长抑制率分别为: (30 ± 13) %(74 ± 22) % (86 ± 26) %, HT-1080移植瘤的生长均具有显著抑制作用; 其中, Fab'-LDM偶联物的抑瘤率最高, LDM组相比有显著差异 (P = 0.045)Fab'-LDM偶联物在体内和体外均对肿瘤侵袭转移有抑制作用, 有望成为新型抗肿瘤侵袭转移的生物治疗剂。

     

    Abstract:

    This study is to investigate the tumor invasion and metastasis inhibition effects of the immunoconjugate composed of lidamycin and anti-type IV collagenase monoclonal antibody Fab' fragment.  Boyden chamber assay was used to evaluate the influence of Fab'-LDM on HT-1080 cells invasion ability, gelatinase spectrum was used to measure the change of invasion factor MMP-2 and MMP-9’s secretion, and RT-PCR was adopted to determine TIMP-1 mRNA expression level.  The immunoconjugate inhibition of tumor in situ metastasis was also tested in nude mice.  The Fab'-LDM conjugates had dose-dependent inhibition effect on HT-1080 cells’ invasion.  At the concentrations of 5 and 10 nmol·L−1, the Fab'-LDM inhibited the invasion by (60 ± 12) % and (79 ± 11) % respectively.  At the concentration of 5 and 10 nmol·L−1, the Fab'-LDM inhibited the secretion of MMP-2 by (42 ± 8) % and (54 ± 6) % and that of MMP-9 by (57 ± 3) % and (87 ± 1) %, respectively.  RT-PCR indicated that conjugates increased the anti-invasion factor TIMP-1 level.  The in vivo experiment showed   that, compared with the control group, the tumor inhibition rate in Fab', Fab'-LDM, and LDM group equaled to (30 ± 13) %, (86 ± 26) %, (74 ± 22) % respectively.  In conclusion, Fab'-LDM could inhibit the invasion and metastasis of tumor and it might be a new tumor biotherapy agent.

     

/

返回文章
返回