Department of Oncology, the Second Affiliated Hospital, Xi'an Jiaotong University, No. 157, Xiwu Road, Xi'an, Shaanxi 710004, PR China.
Department of Pathology, Xi'an Jiaotong University Health Science Center, No. 76, Yanta West Road, Xi'an, Shaanxi 710061, PR China.
Bioorg Med Chem. 2021 Feb 1;31:115986. doi: 10.1016/j.bmc.2020.115986. Epub 2020 Dec 30.
Sinomenine is an alkaloid derived from Chinese medicinal plant Sinomenium acutum. Our previous studies suggested that sinomenine can inhibit the metastasis of breast cancer. However, whether sinomenine can inhibit the metastasis characteristics of breast cancer side population (SP) cells is still unknown. In present study, we isolated the side population (SP) cells from MDA-MB-231 cells by fluorescence-activated cell sorting (FACS). MDA-MB-231 SP cells were treated with different concentrations of sinomenine at the absence or presence of hypoxia, and cell viability were measured by CCK-8 assay. The transwell invasive assay were conducted to assess of the effect of sinomenine on the invasion of hypoxic MDA-MB-231 SP cells. The protein expression was detected by Western blot assay. Sinomenine inhibited the cell viability and invasion of hypoxic MDA-MB-231 SP cells. Western blot assay results showed that the upregulation of MMP-2 and MMP-9 by hypoxia was inversed by sinomenine. Additionally, it was found that sinomenine suppressed the activation of PI3K/Akt/mTOR pathway under hypoxia in MDA-MB-231 SP cells. Moreover, the inhibiton of sinomenine on metastasis of hypoxic MDA-MB-231SP cells and PI3K/Akt/mTOR pathway could be rescued by PI3K activator IGF-1. Our study suggested that sinomenine inhibits invasion of breast cancer SP cells under hypoxia through PI3K/Akt/mTOR pathway.
青藤碱是从中国药用植物青风藤中提取的一种生物碱。我们之前的研究表明，青藤碱可以抑制乳腺癌的转移。然而，青藤碱是否能抑制乳腺癌侧群（SP）细胞的转移特征尚不清楚。在本研究中，我们通过荧光激活细胞分选（FACS）从 MDA-MB-231 细胞中分离侧群（SP）细胞。在缺氧的情况下，用不同浓度的青藤碱处理 MDA-MB-231 SP 细胞，通过 CCK-8 法测定细胞活力。通过 Transwell 侵袭实验评估青藤碱对缺氧 MDA-MB-231 SP 细胞侵袭的影响。通过 Western blot 检测蛋白表达。青藤碱抑制缺氧 MDA-MB-231 SP 细胞的活力和侵袭。Western blot 检测结果表明，青藤碱逆转了缺氧对 MMP-2 和 MMP-9 的上调。此外，还发现青藤碱在缺氧条件下抑制了 MDA-MB-231 SP 细胞中 PI3K/Akt/mTOR 通路的激活。此外，PI3K 激活剂 IGF-1 可挽救青藤碱对缺氧 MDA-MB-231SP 细胞转移和 PI3K/Akt/mTOR 通路的抑制作用。我们的研究表明，青藤碱通过 PI3K/Akt/mTOR 通路抑制缺氧条件下乳腺癌 SP 细胞的侵袭。
