The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510120, China.
The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province 510120, China.
Int J Biol Macromol. 2019 Sep 15;137:32-44. doi: 10.1016/j.ijbiomac.2019.06.189. Epub 2019 Jun 25.
Invasion and metastasis of cancerous cells affects the treatment and prognosis of hepatocellular carcinoma (HCC). HIF-1α-induced epithelial-mesenchymal transition (EMT) is a critical process associated with cancer metastasis. Basil polysaccharide (BPS), one of the major active ingredients isolated from Basil (Ocimum basilicum L.), has been identified to possess an antitumor activity for HCC. In our current study, BPS was obtained by water extraction and ethanol precipitation method and the characterization was analyzed through ultraviolet absorption spectra and Fourier-transform infrared spectrum. A CoCl-induced hypoxia model and a HCC cell line-derived xenograft (CDX) model were used to explore the anti-metastasis efficacy and the mechanism that underlies the antitumor activity of BPS. The results showed that hypoxia could facilitate EMT and promote HCC cells migration and/or invasion. Conversely, BPS inhibited the progression and metastasis of tumor, as well as reversed EMT by causing cytoskeletal remodeling under hypoxic conditions. Moreover, BPS alleviated tumor hypoxia by targeting HIF1α, and the mesenchymal markers (β-catenin, N-cadherin and vimentin) were down-regulated, while the epithelial markers (E-cadherin, VMP1 and ZO-1) were up-regulated after BPS treatment under hypoxic conditions. Thus, these results suggested that BPS may be a valuable option for use in clinical treatment of HCC and other malignant tumors.
癌细胞的侵袭和转移会影响肝癌(HCC)的治疗和预后。HIF-1α 诱导的上皮间质转化(EMT)是与癌症转移相关的关键过程。从罗勒(Ocimum basilicum L.)中分离出的主要活性成分之一的罗勒多糖(BPS)已被确定对 HCC 具有抗肿瘤活性。在本研究中,通过水提法和乙醇沉淀法获得 BPS,并通过紫外吸收光谱和傅里叶变换红外光谱对其进行了表征。采用 CoCl 诱导的缺氧模型和肝癌细胞系衍生的异种移植(CDX)模型,探讨了 BPS 的抗转移功效及其抗肿瘤活性的作用机制。结果表明,缺氧可促进 EMT 并促进 HCC 细胞迁移和/或侵袭。相反,BPS 抑制肿瘤的进展和转移,并通过在缺氧条件下引起细胞骨架重塑来逆转 EMT。此外,BPS 通过靶向 HIF1α 减轻肿瘤缺氧,并且在缺氧条件下用 BPS 处理后,间充质标记物(β-catenin、N-cadherin 和 vimentin)下调,而上皮标记物(E-cadherin、VMP1 和 ZO-1)上调。因此,这些结果表明,BPS 可能是 HCC 和其他恶性肿瘤临床治疗的一种有价值的选择。