Preclinical Studies of Chiauranib Show It Inhibits Transformed Follicular Lymphoma through the VEGFR2/ERK/STAT3 Signaling Pathway

Transformed follicular lymphoma (t-FL), for which there is no efficient treatment strategy, has a rapid progression, treatment resistance, and poor prognosis, which are the main reasons for FL treatment failure. In this study, we identified a promising therapeutic approach with chiauranib, a novel orally developed multitarget inhibitor targeting VEGFR/Aurora B/CSF-1R. We first determined the cytotoxicity of chiauranib in t-FL cell lines through CCK-8, EdU staining, flow cytometry, and transwell assays. We also determined the killing effect of chiauranib in a xenograft model. More importantly, we identified the underlying mechanism of chiauranib in t-FL tumorigenesis by immunofluorescence and Western blotting. Treatment with chiauranib significantly inhibited cell growth and migration, promoted apoptosis, induced cell cycle arrest in G2/M phase, and resulted in significant killing in vivo. Mechanistically, chiauranib suppresses the phosphorylation level of VEGFR2, which has an anti-t-FL effect by inhibiting the downstream MEK/ERK/STAT3 signaling cascade. In conclusion, chiauranib may be a potential therapy to treat t-FL, since it inhibits tumor growth and migration and induces apoptosis by altering the VEGFR2/ERK/STAT3 signaling pathway.

Automated summary

Transformed follicular lymphoma (t-FL) is a disease with no effective treatment strategy and has a rapid progression, treatment resistance, and poor prognosis. In this study, we found a promising therapeutic approach with chiauranib, a multitarget inhibitor targeting VEGFR/Aurora B/CSF-1R. Chiauranib significantly inhibited cell growth and migration, induced apoptosis, and caused cell cycle arrest in the G2/M phase in t-FL. Mechanistically, chiauranib suppressed the phosphorylation level of VEGFR2 and inhibited the downstream MEK/ERK/STAT3 signaling cascade.