使用抗 Epcam 和抗 VEGFR2 纳米抗体联合治疗抑制病理性血管生成。

Efficient Inhibition of Pathologic Angiogenesis using Combination Therapy of Anti-Epcam and Anti-VEGFR2 Nanobodies.

机构信息

Biotechnology Department, Venom and Biotherapeutics Molecules Laboratory, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.

Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

出版信息

Curr Pharm Des. 2023;29(13):1059-1066. doi: 10.2174/1381612829666230420083431.

DOI:10.2174/1381612829666230420083431

PMID:37078346

Abstract

BACKGROUND

EpCAM and VEGFR2 play an important role in angiogenesis and tumorigenesis. It is currently of paramount importance to produce new drugs that can inhibit the angiogenesis and proliferation of tumor cells. Nanobodies are potential drug candidates for cancer therapy due to their unique properties.

OBJECTIVE

This study aimed to investigate the combined inhibitory effect of anti-EpCAM and anti-VEGFR2 nanobodies in cancer cell lines.

METHODS

Inhibitory activity of anti-EpCAM and anti-VEGFR2 nanobodies on MDA-MB231, MCF7, and HUVEC cells was investigated using both in vitro (MTT, migration, and tube formation assays) and in vivo assays.

RESULTS

Results showed that the combination of anti-EpCAM and anti-VEGFR2 nanobodies efficiently inhibited proliferation, migration, and tube formation of MDA-MB-231 cells compared to each individual nanobodies (p < 0.05). In addition, the combination of anti-EpCAM and anti-VEGFR2 nanobodies efficiently inhibited tumor growth and volume of Nude mice bearing MDA-MB-231 cells (p < 0.05).

CONCLUSION

Taken together, the results indicate the potential of combination therapy as an efficient approach to cancer therapy.

摘要

背景

EpCAM 和 VEGFR2 在血管生成和肿瘤发生中起着重要作用。目前，生产能够抑制肿瘤细胞血管生成和增殖的新药至关重要。由于纳米抗体具有独特的性质，因此它们是癌症治疗的潜在药物候选物。

目的

本研究旨在探讨抗 EpCAM 和抗 VEGFR2 纳米抗体在癌细胞系中的联合抑制作用。

方法

使用体外（MTT、迁移和管形成测定）和体内测定研究了抗 EpCAM 和抗 VEGFR2 纳米抗体对 MDA-MB231、MCF7 和 HUVEC 细胞的抑制活性。

结果

结果表明，与单独的纳米抗体相比，抗 EpCAM 和抗 VEGFR2 纳米抗体的组合可有效抑制 MDA-MB-231 细胞的增殖、迁移和管形成（p<0.05）。此外，抗 EpCAM 和抗 VEGFR2 纳米抗体的组合可有效抑制荷 MDA-MB-231 细胞的 Nude 小鼠的肿瘤生长和体积（p<0.05）。