Department of Pharmacy, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China.
Department of Radiation Oncology of the Clinical Cancer Center, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, People's Republic of China.
Biofactors. 2020 Jul;46(4):620-628. doi: 10.1002/biof.1627. Epub 2020 Feb 20.
Colorectal cancer (CRC) refers to a deadly carcinoma following potent invasiveness and metastasis in advanced stage. Unfortunately, existing anti-CRC medicine is insufficient for chemotherapy in addition to adverse effects. Consequently, the candidate natural ingredient for treating CRC needs to be further developed. Our previous experiments report that genistein exerts beneficial effects to inhibit CRC cells via an antiproliferative mechanism. Based on the metastatic characteristics of staging CRC, anti-invasive and antimetastatic pharmacological activities using genistein remain uninvestigated. The scientific purpose of this study was to disclose the antimetastatic mechanism by using human and cell culture/nude mice samples, followed by biochemical tests and immunoassays. In human study, these CRC cases resulted in increased transforming growth factor beta-1 (TGF-β1) levels, long noncoding RNA (lncRNA) TTTY18 expressions, followed with up-regulated Ki-67, serum and glucocorticoid regulated kinase 1 (SGK1), Akt expressions. In a study in vitro, genistein-dosed CRC cells showed suppressed cell viability, promoted cell apoptosis, reduced Ki-67 positive cells, reduced cellular migration, down-regulated expressions of TTTY18, SGK1, Akt , p38 MAPK . In a further study in vivo, genistein-dosed tumor-bearing nude mice exhibited visibly reduced body mass, lowered tumorous TGF-β1 and TTTY18 contents. In addition, intracellular numbers of SGK1, Akt , p38 MAPK positive cells were reduced dose-dependently. Collectively, these human and experimentative findings reveal that genistein pharmacologically exerts the potential antimetastatic CRC effects, possibly through a molecular mechanism of inhibiting TTTY18/Akt pathway in CRC cells.
结直肠癌（CRC）是一种致命的癌，在晚期具有很强的侵袭性和转移性。不幸的是，现有的抗 CRC 药物除了有不良反应外，对化疗也不够有效。因此，需要进一步开发治疗 CRC 的候选天然成分。我们之前的实验报告称，染料木黄酮通过抗增殖机制对抑制 CRC 细胞具有有益作用。基于 CRC 的转移性特征，使用染料木黄酮的抗侵袭和抗转移药理活性尚未得到研究。本研究的科学目的是通过使用人及细胞培养/裸鼠样本，进行生化测试和免疫测定，揭示其抗转移机制。在人类研究中，这些 CRC 病例导致转化生长因子β-1（TGF-β1）水平升高，长链非编码 RNA（lncRNA）TTTY18 表达增加，随后 Ki-67、血清和糖皮质激素调节激酶 1（SGK1）、Akt 表达上调。在体外研究中，染料木黄酮处理的 CRC 细胞表现出细胞活力降低、促进细胞凋亡、Ki-67 阳性细胞减少、细胞迁移减少、TTTY18、SGK1、Akt、p38 MAPK 表达下调。在进一步的体内研究中，染料木黄酮处理的荷瘤裸鼠表现出明显的体重减轻、肿瘤 TGF-β1 和 TTTY18 含量降低。此外，SGK1、Akt、p38 MAPK 阳性细胞的细胞内数量呈剂量依赖性减少。综上所述，这些人体和实验研究结果表明，染料木黄酮在药理学上具有抑制 CRC 细胞 TTTY18/Akt 通路的潜在抗转移作用，可能是通过一种分子机制。
