Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3.
Anti-IGF-1R monoclonal antibody inhibits the carcinogenicity activity of acquired trastuzumab-resistant SKOV3.
复制标题
抗 IGF-1R 单克隆抗体可抑制获得性曲妥珠单抗耐药 SKOV3 的致癌活性。
DOI：
10.1186/s13048-014-0103-5
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发表时间：
2014-11-26
影响因子：
4
通讯作者：
Qiao C
中科院分区：
文献类型：
--
作者：
Wang W;Zhang Y;Lv M;Feng J;Peng H;Geng J;Lin Z;Zhou T;Li X;Shen B;Ma Y;Qiao C
抗体耐药不仅存在于原发病例中，也存在于获得性病例中，且与生存率低、复发风险高有关。逆转耐药往往能获得更好的临床治疗效果。在此之前，我们建立了一个曲妥珠单抗耐药的卵巢癌细胞系，命名为SKOV 3-T，具有较低的HER 2和诱导较高的IGF-1 R表达水平，以保持细胞存活。IGF-1 R被鉴定为对SKOV 3-T生长重要。然后，利用一种新的抗IGF-1 R单克隆抗体LMAb 1对SKOV 3-T细胞的生长增殖、迁移、克隆形成和体内致癌性进行了抑制。在体外和体内试验中，LMAb 1均显示出有效的抗肿瘤作用，尤其是与曲妥珠单抗联合使用时，有利于延长小鼠的生存时间以及减小肿瘤。初步证实抗体的作用机制可能是通过抑制IGF-1 R的活化及下游MAPK、AKT通路的转导。我们在曲妥珠单抗耐药的卵巢癌模型中使用曲妥珠单抗联合LMAb 1获得了令人满意的抗肿瘤活性。在类似的情况下，无论是获得性的，还是从头开始的，使用联合抗体治疗策略可能会取得良好的疗效。
Antibody resistance, not only de novo but also acquired cases, usually exists and is related with lower survival rate and high risk of recurrence. Reversing the resistance often results in better clinical therapeutic effect. Previously, we established a trastuzumab-resistant ovarian cancer cell line, named as SKOV3-T, with lower HER2 and induced higher IGF-1R expression level to keep cell survival. IGF-1R was identified important for SKOV3-T growth. Then, a novel anti-IGF-1R monoclonal antibody, named as LMAb1, was used to inhibit SKOV3-T in cell growth/proliferation, migration, clone formation and in vivo carcinogenicity. In both in vitro and in vivo assays, LMAb1 showed effective anti-tumor function, especially when being used in combination with trastuzumab, which was beneficial to longer survival time of mice as well as smaller tumor. It was also confirmed preliminarily that the mechanism of antibody might be to inhibit the activation of IGF-1R and downstream MAPK, AKT pathway transduction. We achieved satisfactory anti-tumor activity using trastuzumab plus LMAb1 in trastuzumab-resistant ovarian cancer model. In similar cases, not only acquired but also de novo, good curative effect might be achieved using combined antibody therapy strategies.
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DOI：
10.1158/1078-0432.ccr-13-3448
发表时间：
2014-06-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Beltran PJ;Calzone FJ;Mitchell P;Chung YA;Cajulis E;Moody G;Belmontes B;Li CM;Vonderfecht S;Velculescu VE;Yang G;Qi J;Slamon DJ;Konecny GE
通讯作者：
Konecny GE
影响因子：
50.3
作者：
Agus, DB;Akita, RW;Sliwkowski, MX
通讯作者：
Sliwkowski, MX
影响因子：
11.5
作者：
Atzori, Francesco;Tabernero, Josep;Baselga, Jose
通讯作者：
Baselga, Jose
影响因子：
56.9
作者：
Cui, HM;Cruz-Correa, M;Feinberg, AP
通讯作者：
Feinberg, AP
影响因子：
50.5
作者：
De Roock, W.;Piessevaux, H.;Tejpar, S.
通讯作者：
Tejpar, S.