Colorectal cancer (CRC) is the second leading cause of cancer-related deaths. Tumor angiogenesis plays a critical role in CRC metastasis, and hypoxia, which widely existed in the tumor mass, drives tumor angiogenesis. Sesamin, a phytochemical derived from sesame seeds, has been reported to inhibit tumor cell growth and metastasis, however, the role of sesamin in CRC angiogenesis and its underlying mechanism have not been investigated yet. Here, an in vitro tube formation assay and an in vivo angiogenesis assay were used to explore the role of sesamin in CRC angiogenesis. In this study, we found that sesamin significantly inhibited hypoxia-stimulated CRC angiogenesis in a dose-dependent manner in vitro. Moreover, oral intake of sesamin dramatically suppressed neovessel formation of matrigel plugs with CRC cells in nude mice. In mechanism, sesamin reduced the expression of VEGFA to inhibit hypoxia-induced CRC angiogenesis. In addition, sesamin inhibited the phosphorylation of IκBα and thus restrained NF-κB p65 to activate HIF-1α transcription under hypoxic conditions. Finally, our results indicated that sesamin inhibited hypoxia-induced CRC angiogenesis via the NF-κB/HIF-1α/VEGFA signaling pathway. Our study might provide a theoretical and experimental basis for the use of sesamin in the prevention and treatment of CRC.

Perfluorooctane sulfonic acid (PFOS), a persistent environmental pollutant, has adverse effects on gestation pregnancy. Peroxisome proliferator-activated receptor γ (PPARγ) is involved in angiogenesis, metabolic processes, anti-inflammatory, and reproductive development. However, the function of PPARγ in PFOS evoked disadvantageous effects on the placenta remain uncertain. Here, we explored the role of PPARγ in PFOS-induced placental toxicity. Cell viability, cell migration, angiogenesis, and mRNA expression were monitored by CCK-8 assay, wound healing assay, tube formation assay, and real-time PCR, respectively. Activation and overexpression of PPARγ were conducted by rosiglitazone or pcDNA-PPARγ, and inhibition and knockdown of PPARγ were performed by GW9662 or si-PPARγ. Results revealed that PFOS decreased cell growth, migration, angiogenesis, and increased inflammation in human HTR-8/SVneo and JEG-3 cells. Placenta diameter and fetal weight decreased in mice treated with PFOS (12.5 mg/kg). In addition, rosiglitazone or pcDNA-PPARγ rescued cell proliferation, migration, angiogenesis, and decreased inflammation induced by PFOS in HTR8/SVneo and JEG-3 cells. Furthermore, GW9662 or si-PPARγ exacerbated the inhibition of cell viability, migration, angiogenesis, and aggravated inflammation induced by PFOS in HTR-8/SVneo and JEG-3 cells. Meanwhile, the results of mRNA expression level were consistent with the cell representation. In conclusion, our findings revealed that PFOS induced placenta cell toxicity and functional damage through PPARγ pathway.