School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; Department of Nutrition, I-Shou University, Kaohsiung 84001, Taiwan.
School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan.
Biomed Pharmacother. 2022 Aug;152:113219. doi: 10.1016/j.biopha.2022.113219. Epub 2022 Jun 9.
Metastasis is a major challenge in aggressive endometrial cancer treatment accounting for the high recurrence risk and poor prognosis of epithelial-mesenchymal transition (EMT), regulated by the transforming growth factor beta (TGFβ) signaling pathway, facilitates tumor metastasis. Spirulina phycocyanin extract (SPE) and its purified products allophycocyanin (APC) and C-phycocyanin (C-PC), derived from Spirulina platensis, can be considered a nutraceutical compound with the ability to inhibit tumor growth and metastasis. Current study aims to investigate the anti-metastatic potential of SPE, and its purified products APC, and C-PC on endometrial cancer both in vitro and in vivo. Firstly, human endometrial cancer cell lines (HEC-1A and Ishikawa) as an in vitro model. Secondly, HEC-1A cells transfected with luminescence gene were implanted into female nude mice as a xenograft model. MTT assay, transwell migration assay, immunoblotting assay, quantitative real-time polymerase chain reaction assay, and IVIS XRMS analysis techniques were used. The in vitro results showed that SPE and its purified products APC and C-PC inhibited cell migration, and altered the expression of EMT-related phenotypes by reversing the TGFβ/SMADs signaling pathway. The in vivo results indicated that SPE repressed the metastasis of HEC-1A-LUC cells through modulating EMT-related markers expression. Overall, SPE and its efficient components APC and C-PC reversed the EMT through targeting the TGFβ/SMADs signaling pathway, suggesting an effective therapeutic strategy for metastatic endometrial cancer.
转移是侵袭性子宫内膜癌治疗的主要挑战，其上皮-间充质转化（EMT）的高复发风险和不良预后与转化生长因子β（TGFβ）信号通路的调节有关，促进了肿瘤转移。来源于螺旋藻的螺旋藻藻蓝蛋白提取物（SPE）及其纯化产物藻蓝蛋白（APC）和 C 藻蓝蛋白（C-PC）可被视为具有抑制肿瘤生长和转移能力的营养化合物。本研究旨在研究 SPE 及其纯化产物 APC 和 C-PC 对子宫内膜癌的体内外抗转移潜力。首先，用人子宫内膜癌细胞系（HEC-1A 和 Ishikawa）作为体外模型。其次，将发光基因转染的 HEC-1A 细胞植入雌性裸鼠作为异种移植模型。采用 MTT 测定法、Transwell 迁移测定法、免疫印迹测定法、实时定量聚合酶链反应测定法和 IVIS XRMS 分析技术。体外结果表明，SPE 及其纯化产物 APC 和 C-PC 通过逆转 TGFβ/SMADs 信号通路抑制细胞迁移，并改变 EMT 相关表型的表达。体内结果表明，SPE 通过调节 EMT 相关标志物的表达抑制了 HEC-1A-LUC 细胞的转移。总的来说，SPE 及其有效成分 APC 和 C-PC 通过靶向 TGFβ/SMADs 信号通路逆转 EMT，为转移性子宫内膜癌提供了一种有效的治疗策略。
