Reduced RAC1 activity inhibits cell proliferation and induces apoptosis in neurofibromatosis type 2(NF2)-associated schwannoma

Abstract

Objective

To study the function and potential mechanism of RAC1 inhibitors in NF2-associated schwannoma.

Methods

In this study, we the downregulation of RAC1 activity and tumor cell phenotypes by RAC1 inhibitor NSC23766 in vitro. And we further validated the anti-proliferation effect by this RAC1 inhibitor in subcutaneous xenograft tumor model and sciatic nerve model.

Results

Pharmacological inhibition of RAC1 could significantly inhibit the proliferation of both RT4 cells and human NF2-associated primary schwannoma cells by inducing apoptosis. Pharmacological inhibition of RAC1 effectively reduced Rac1 activity and down-regulated the pathway downstream of Rac. Moreover, pharmacological inhibition of RAC1 showed a potential antitumor effect, with low toxicity in vivo.

Conclusion

RAC1 inhibitors may play a therapeutic role in patients with schwannoma.

Keywords:

• Apoptosis
• neurofibromatosis type 2 (NF2)
• RAC1
• schwannoma
• toxicity