Loureirin A, derived from Dragon's blood, promoted drug delivery and efficacy in pancreatic cancer via vascular promotion.

Chemotherapy is a mainstream treatment for pancreatic cancer. Unfortunately, it exhibits a marginal efficacy, partly because the sparse and dysfunctional vasculature in pancreatic cancer has substantially prevented the delivery of chemotherapeutic agents to tumor cells. Vascular promotion, which directs newly generated vessels into previously hypovascular regions, represents an appealing strategy to enhance drug perfusion to the tumor. Currently, only a limited number of vascular-promoting agents have been reported, yet they still exhibit undesirable properties. Dragon's blood is well known for its vascular regulatory activity, which promotes blood circulation and disperses blood stasis. However, it remains unclear whether and which components of Dragon's blood promote tumor angiogenesis. Herein, we revealed that loureirin A (LA) could activate multiple steps of angiogenesis in vitro, including promoting the proliferation, migration, and tube formation of vascular endothelial cells (ECs). Furthermore, the proangiogenic activity of LA was primarily due to its stimulation of the vascular endothelial growth factor (VEGF) secretion by ECs. In tumor-bearing mice, the combination with LA considerably enhanced the antitumor efficacy of gemcitabine without causing additional side effects. Further exploration revealed that LA enhanced tumor angiogenesis and vascular function, thereby increasing drug delivery and alleviating tumor hypoxia. Collectively, this work provides a naturally derived vascular-promoting agent for the treatment of hypovascular pancreatic cancer.