Gene silencing of indoleamine 2,3-dioxygenase hinders tumor growth through angiogenesis inhibition

Abstract The significance of indoleamine 2,3-dioxygenase-1 (IDO1) has been studied in various types of tumors, but the relationship between IDO1 and tumor angiogenesis needs further delineation. We aimed to clarify the relationship between tumor angiogenesis and IDO1 expression, and to explore the possibility of IDO1-targeting molecular therapy for lung cancer. For the first time, we found that silencing the IDO1 gene using small interfering RNA (siRNA) inhibits in vitro cancer cell invasion and migration. We further demonstrated that knockdown of IDO1 decreased the formation of vasculogenic mimicry. In addition to these in vitro findings, we also demonstrated that in vivo IDO1 gene silencing using short hairpin RNA (shRNA) delayed tumor onset and inhibited tumor growth in the mouse model. Immunostaining showed that IDO1 gene silencing inhibited tumor angiogenesis. Moreover, the expression of IDO1 was associated with microvessel density (MVD) labeled by CD34 and CD146. These findings indicate that IDO1 has the potential to participate in or contribute to the formation of new capillaries, supporting the applicability of IDO1-targeting molecular therapy in lung cancer.