| Description |
Dalotuzumab (MK-0646) is a recombinant humanized monoclonal antibody (IgG1 type) targeting IGF-1R. Dalotuzumab acts by inhibiting IGF-1- and IGF-2-mediated tumor cell proliferation, IGF-1R autophosphorylation, and Akt phosphorylation. Dalotuzumab also induces Apoptosis and cycle arrest. Dalotuzumab in combination with other anticancer drugs such as statins can enhance the antitumor activity of Dalotuzumab in vitro and in vivo[1][2][3].
|
| Related Catalog |
|
| In Vitro |
Dalotuzumab (h7C10; 33 nM; 24 h) 抑制 IGF-1 和 IGF-2 诱导的 MCF7 雌激素依赖性乳腺癌细胞增殖，IC>sub>50 值分别为 4.2 和 3.1 nM[1]。 Dalotuzumab (33 nM; 24 h) 在 IGF-1 诱导的 MCF7 细胞中，诱导周期停滞，并抑制 IGF-IR 和 IRS-1 的自磷酸化[1]。 Dalotuzumab 使 NK 细胞介导的 MCF7 和 A459 细胞的裂解率分别提高了 26% 和 25%[1]。 Dalotuzumab (MK-0646; 10 µg/mL; 24, 48 h) 消除 IGF1 在子宫内膜癌细胞中的抗凋亡作用[2]。 Cell Proliferation Assay[1] Cell Line: MCF7 cells (IGF-1 and IGF-2-induced) Concentration: 33 nM Incubation Time: 24 h Result: Showed anti-proliferation activity to IGF-1- and IGF-2-induced MCF7, with IC50 values of 4.2 and 3.1 nM, respectively. Cell Cycle Analysis[1] Cell Line: MCF7 cells (IGF-1-induced) Concentration: 33 nM Incubation Time: 24 h Result: Prevented cell cycle progression from the G1 to S and G2/M phases. Apoptosis Analysis[2] Cell Line: ECC-1 and USPC-1 cells (IGF-1-induced) Concentration: 10 µg/mL Incubation Time: 24, 48 h Result: Reversed the effect of IGF1 on caspase-3 cleavage (Caspase-3 is activated in apoptotic cells and cleaves several cellular proteins, including PARP). Western Blot Analysis[1] Cell Line: MCF7 cells (IGF-1-induced) Concentration: 33 nM Incubation Time: 24 h Result: Led to a decrease of phosphorylation for both β-chain and IRS-1.
|
| In Vivo |
Dalotuzumab (h7C10; i.p.; 第一次 250 µg/小鼠，然后每周两次 125 µg/小鼠，持续 40 天) 显示对 MCF-7 和 A549 异种移植肿瘤模型的抗肿瘤作用[1]。 Animal Model: Swiss Nude mice (MCF-7 and A549 xenograft tumor models)[1]. Dosage: 125 and 250 (first time) µg/mice Administration: Intraperitoneal injection; 250 µg/mice for the first time, then 125 µg/mice twice weekly for 40 days Result: Led to average tumor volume at 6 weeks post-cell injection was reduced by 70% and 72% in the MCF-7 and A549 models, respectively.
|
| References |
[1]. Goetsch L, et al. A recombinant humanized anti-insulin-like growth factor receptor type I antibody (h7C10) enhances the antitumor activity of vinorelbine and anti-epidermal growth factor receptor therapy against human cancer xenografts. Int J Cancer. 2005 Jan 10;113(2):316-28. [2]. Bitelman C, et al. IGF1R-directed targeted therapy enhances the cytotoxic effect of chemotherapy in endometrial cancer. Cancer Lett. 2013 Jul 10;335(1):153-9. [3]. Scartozzi M, et al. Dalotuzumab, a recombinant humanized mAb targeted against IGFR1 for the treatment of cancer. Curr Opin Mol Ther. 2010 Jun;12(3):361-71.
|
