Zhou Jin, Jiang Yuan-Yuan, Wang Xiao-Xia, Wang Hai-Ping, Chen Huan, Wu Yi-Chao, Wang Long, Pu Xiang, Yue Gui-Zhou, Zhang Li
College of Science, Sichuan Agricultural University, Ya'an, China.
College of Life Science, China West Normal University, Nanchong, China.
Ann Transl Med. 2020 Oct;8(20):1295. doi: 10.21037/atm-20-5741.
In Chinese herbal medicine, Tanshinone IIA (Tan-IIA) is one of the main compounds extracted from Bunge. Tan-IIA has been demonstrated to inhibit the growth of various tumors. However, the detailed molecular and cellular mechanisms of the antitumor effect of Tan-IIA have yet to be fully illuminated.
A2780 and ID-8 were treated with 0, 1.2, 2.4, 4.8, or 9.6 µg/mL Tan-IIA for 24 hours. Cell counting Kit-8 assay and EdU staining were used to evaluate cell proliferation. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and flow cytometry were performed to analyze apoptosis. Western blot was carried out to determine the protein levels. Flow cytometry was used for cell cycle analysis. The levels of mRNA expression were analyzed by real-time polymerase chain reaction. The anti-tumor effect of Tan-IIA was observed in a tumor-bearing mouse model.
Tan-IIA inhibited the proliferation of ovarian cancer cells in a dose-dependent manner by inducing G2/M phase arrest. It also down-regulated B-cell lymphoma 2 (Bcl-2) and up-regulated Bcl-2-associated X protein (Bax) in ovarian cancer cells to induce apoptosis, and suppressed cell migration by inhibiting focal adhesion kinase phosphorylation. Tan-IIA significantly reduced vascular endothelial growth factor (VEGF) and cyclooxygenase-2 (COX2) mRNA expression in ovarian cancer cells. , Tan-IIA significantly inhibited tumor growth by inducing apoptosis and promoting anti-angiogenesis.
The results of this study shed light on the molecular and cellular mechanisms for the antitumor effect of Tan-IIA.
在中草药中,丹参酮IIA(Tan-IIA)是从丹参中提取的主要化合物之一。Tan-IIA已被证明可抑制多种肿瘤的生长。然而,Tan-IIA抗肿瘤作用的详细分子和细胞机制尚未完全阐明。
将A2780和ID-8细胞分别用0、1.2、2.4、4.8或9.6μg/mL的Tan-IIA处理24小时。采用细胞计数试剂盒-8法和EdU染色法评估细胞增殖。进行末端脱氧核苷酸转移酶dUTP缺口末端标记(TUNEL)检测和流式细胞术分析细胞凋亡。采用蛋白质免疫印迹法测定蛋白水平。流式细胞术用于细胞周期分析。通过实时聚合酶链反应分析mRNA表达水平。在荷瘤小鼠模型中观察Tan-IIA的抗肿瘤作用。
Tan-IIA通过诱导G2/M期阻滞以剂量依赖性方式抑制卵巢癌细胞的增殖。它还下调卵巢癌细胞中的B细胞淋巴瘤2(Bcl-2)并上调Bcl-2相关X蛋白(Bax)以诱导凋亡,并通过抑制粘着斑激酶磷酸化来抑制细胞迁移。Tan-IIA显著降低卵巢癌细胞中血管内皮生长因子(VEGF)和环氧合酶-2(COX2)的mRNA表达。Tan-IIA通过诱导凋亡和促进抗血管生成显著抑制肿瘤生长。
本研究结果揭示了Tan-IIA抗肿瘤作用的分子和细胞机制。