RETRACTED ARTICLE: Nuciferine inhibits the progression of glioblastoma by suppressing the SOX2-AKT/STAT3-Slug signaling pathway

Abstract

Background Nuciferine (NF), extracted from the leaves of N. nucifera Gaertn , has been shown to exhibit anti-tumor and anti-viral pharmacological properties. It can also penetrate the blood brain barrier (BBB). However, the mechanism by which NF inhibits glioblastoma (GBM) progression is not well understood. We aimed to determine the anti-tumor effect of NF on GBM cell lines and clarify the potential molecular mechanism involved. Methods U87MG and U251 cell lines were used in vitro to assess the anti-tumor efficacy of NF. Cytotoxicity, viability, and proliferation were evaluated by MTT and colony formation assay. After Annexin V-FITC and PI staining, flow cytometry was performed to evaluate apoptosis and cell cycle changes in NF-treated GBM cells. Wound healing and Transwell assays were used to assess migration and invasion of GBM cells. Western blot analysis, immunofluorescence staining, immunohistochemistry, and bioinformatics were used to gain insights into the molecular mechanisms. Preclinical therapeutic efficacy was mainly estimated by ultrasound and MRI in xenograft nude mouse models. Results NF inhibited the proliferation, mobility, stemness, angiogenesis, and epithelial-to-mesenchymal transition (EMT) of GBM cells. Additionally, NF induced apoptosis and G2 cell cycle arrest. Slug expression was also decreased by NF via the AKT and STAT3 signaling pathways. Interestingly, we discovered that NF affected GBM cells partly by targeting SOX2, which may be upstream of the AKT and STAT3 pathways. Finally, NF led to significant tumor control in GBM xenograft models. Conclusions NF inhibited the progression of GBM via the SOX2-AKT/STAT3-Slug signaling pathway. SOX2-targeting with NF may offer a novel therapeutic approach for GBM treatment. Electronic supplementary material The online version of this article (10.1186/s13046-019-1134-y) contains supplementary material, which is available to authorized users.

LTBP1 plays a potential bridge between depressive disorder and glioblastoma

“…And in order to con rm the case, we evaluated the expression of epithelial and mesenchymal markers in high and low LTBP1 group and found a higher expression of mesenchymal markers such as vimentin and CD44, as well as lower expression of typical epithelial markers such as Ecadherin, in high LTBP1 group. Moreover, ow cytometry cell cycle assay revealed a higher proportion of S and G2-M phases in LTBP1 high expression group, which was reported by many other researches to be an important feature of EMT in many type of cancers, including GBM [64][65][66]. As for the reason why no expression differences of SOX1 was observed between the two group, we suppose that SOX1 is a transcription factor that expressed almost in all tissue and cells with high proliferative rate and stemness.…”

LTBP1 plays a potential bridge between depressive disorder and glioblastoma

“…The changing of ECM by LTBP1 could function as an indicator of depressive/anxiety disorder and GBM by regulating inflammatory responses. And in order to confirm the case, we evaluated the expression of epithelial and mesenchymal markers in high and low LTBP1 group and found a higher Moreover, flow cytometry cell cycle assay revealed a higher proportion of S and G2-M phases in LTBP1 high expression group, which was reported by many other researches to be an important feature of EMT in many type of cancers, including GBM [64][65][66]. As for the reason why no expression differences of SOX1 was observed between the two group, we suppose that SOX1 is a transcription factor that expressed almost in all tissue and cells with high proliferative rate and stemness.…”

Role of STAT3 signaling pathway in breast cancer

“…Matrix metallopeptidases (MMPs) are known to play important roles in breast cancer metastasis. A wellstudied mechanism of STAT3-mediated cell metastasis is through upregulating MMP2, MMP9, Twist, Snail, Slug and vimentin [47][48][49]. Ma et al have reported that inhibition of STAT3 phosphorylation could reduce the expression of vasodilator-stimulated phosphoprotein (VASP), MMP2 and MMP9 in breast cancer [50].…”