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Eltrombopag Inhibits Metastasis in Breast Carcinoma by Targeting HuR Protein

Eltrombopag is a small molecule TPO-R agonist that has been shown in our previous studies to inhibit tumor growth by targeting Human antigen R (HuR) protein. HuR protein not only regulates the mRNA stability of tumor growth-related genes, but it also regulates the mRNA stability of a variety of cancer metastasis-related genes, such as Snail, Cox-2, and Vegf-c. However, the role and mechanisms of eltrombopag in breast cancer metastasis have not been fully investigated. The purpose of this study was to investigate whether eltrombopag can inhibit breast cancer metastasis by targeting HuR. Our study first found that eltrombopag can destroy HuR-AU-rich element (ARE) complexes at the molecular level. Secondly, eltrombopag was found to suppress 4T1 cell migration and invasion and inhibit macrophage-mediated lymphangiogenesis at the cellular level. In addition, eltrombopag exerted inhibitory effects on lung and lymph node metastasis in animal tumor metastasis models. Finally, it was verified that eltrombopag inhibited the expressions of Snail, Cox-2, and Vegf-c in 4T1 cells and Vegf-c in RAW264.7 cells by targeting HuR. In conclusion, eltrombopag displayed antimetastatic activity in breast cancer in an HuR dependent manner, which may provide a novel application for eltrombopag, hinting at the multiple effects of HuR inhibitors in cancer therapy.

 

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The study aimed to investigate the potential of eltrombopag in inhibiting breast cancer metastasis by targeting HuR protein. The researchers found that eltrombopag can destroy HuR-AU-rich element (ARE) complexes at the molecular level, which led to the inhibition of the expressions of several cancer metastasis-related genes such as Snail, Cox-2, and Vegf-c. The study also revealed that eltrombopag inhibited 4T1 cell migration and invasion and macrophage-mediated lymphangiogenesis at the cellular level.

Furthermore, the researchers demonstrated that eltrombopag exerted inhibitory effects on lung and lymph node metastasis in animal tumor metastasis models. Finally, it was verified that eltrombopag inhibited the expressions of Snail, Cox-2, and Vegf-c in 4T1 cells and Vegf-c in RAW264.7 cells by targeting HuR. The findings suggest that eltrombopag displayed antimetastatic activity in breast cancer in an HuR-dependent manner, which may provide a novel application for eltrombopag and hint at the multiple effects of HuR inhibitors in cancer therapy.

Related Products

Cat.No. Product Name Information
S2229 Eltrombopag Olamine Eltrombopag Olamine is a member of the biarylhydrazone class, which is a nonpeptide agonist of the thrombopoietin receptor (TpoR).

Related Targets

TpoR