Emodin inhibits angiogenesis in pancreatic cancer by regulating the transforming growth factor-β/drosophila mothers against decapentaplegic pathway and angiogenesis-associated microRNAs

作者：Sheng‐Zhang Lin, Jin‐Bo Xu, Xu Ji, Hui Chen, Hong‐Tao Xu, Ping Hu, Liang Chen, Jing-Qiang Guo, Minyuan Chen, Dian Lu, Zhaohong Wang, Hongfei Tong · 发表于：Molecular Medicine Reports · 年份：2015 · DOI：10.3892/mmr.2015.4158 · 被引用次数：44 · 研究领域：Phytochemistry and biological activity of medicinal plants、Angiogenesis and VEGF in Cancer、Axon Guidance and Neuronal Signaling

Emodin is a traditional Chinese medicine, which has been demonstrated to inhibit the growth of pancreatic cancer cells. However, the underlying molecular mechanisms remain to be elucidated. The present study investigated whether emodin suppresses angiogenesis in pancreatic cancer. A nude mouse pancreatic cancer xenograft model was established using SW1990 human pancreatic cancer cells by surgical orthotopic implantation. Different doses of emodin were injected into the abdominal cavities of the tumor‑bearing mouse models and controls three times each week for 2 weeks. The tumors were measured and weighed, the expression of cluster of differentiation 34 was detected using immunochemistry, and microvessel densities were calculated. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were performed to determine the mRNA and protein expression levels of transforming growth factor (TGF)‑β and drosophila mothers against decapentaplegic (Smad) homologs. The angiogenesis‑associated microRNAs (miR), miR‑20, miR‑155 and miR‑210 were assessed by RT‑qPCR. A negative dose‑dependent association was revealed between treatment with emodin and the volume and weight of tumors and microvessel density. Emodin was associated with lower mRNA and protein expression levels of TGF‑β1 and its downstream target, angiopoietin‑like 4, and higher mRNA and protein expression levels of TGF‑β receptor (TβR)I, TβRII and Smad4. Notably, treatment with emodin was associat...