Ren-Ping Zhao, Sen-Sen Lin, Yuan Sheng-Tao, Yu Bo-Yang, Bai Xian-Shu, Sun Li, Zhang Lu-Yong
Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing 210009, China.
Chin J Nat Med. 2014 Jan;12(1):24-9. doi: 10.1016/S1875-5364(14)60005-4.
To investigate the anticancer activity of DT-13 under normoxia and determine the underlying mechanisms of action.
MDA-MB-435 cell proliferation, migration, and adhesion were performed to assess the anticancer activity of DT-13, a saponin from Ophiopogon japonicus, in vitro. In addition, the effects of DT-13 on tumor growth and metastasis in vivo were evaluated by orthotopic implantation of MDA-MB-435 cells into nude mice; mRNA levels of vascular endothelial growth factor (VEGF), C-C chemokine receptor type 5 (CCR5) and hypoxia-inducible factor 1α (HIF-1α) were evaluated by real-time quantitative PCR; and CCR5 protein levels were detected by Western blot assay.
At 0.01 to 1 μmol·L(-1), DT-13 inhibited MDA-MB-435 cell proliferation, migration, and adhesion significantly in vitro. DT-13 reduced VEGF and CCR5 mRNAs, and decreased CCR5 protein expression by down-regulating HIF-1α. In addition, DT-13 inhibited MDA-MB-435 cell lung metastasis, and restricted tumor growth slightly in vivo.
DT-13 inhibited MDA-MB-435 cell proliferation, adhesion, and migration in vitro, and lung metastasis in vivo by reducing VEGF, CCR5, and HIF-1α expression.
研究常氧条件下DT-13的抗癌活性，并确定其潜在作用机制。
进行MDA-MB-435细胞增殖、迁移和黏附实验，以评估麦冬皂苷DT-13的体外抗癌活性。此外，通过将MDA-MB-435细胞原位植入裸鼠来评估DT-13对体内肿瘤生长和转移的影响；通过实时定量PCR评估血管内皮生长因子（VEGF）、C-C趋化因子受体5型（CCR5）和缺氧诱导因子1α（HIF-1α）的mRNA水平；通过蛋白质印迹法检测CCR5蛋白水平。
在0.01至1μmol·L⁻¹浓度下,DT-13在体外显著抑制MDA-MB-435细胞增殖、迁移和黏附。DT-13降低了VEGF和CCR5的mRNA水平，并通过下调HIF-1α降低了CCR5蛋白表达。此外，DT-13抑制了MDA-MB-435细胞的肺转移，并在体内轻微限制了肿瘤生长。
DT-13通过降低VEGF、CCR5和HIF-1α的表达，在体外抑制MDA-MB-435细胞增殖、黏附和迁移，在体内抑制肺转移。
