Hou Yue, Xu Jinghua, Liu Xia, Xia Xichun, Li Ning, Bi Xiuli
Department of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110004, P.R. China.
Department of Pharmacology, School of Life Science and Biopharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, P.R. China.
Pharmacogn Mag. 2015 Apr-Jun;11(42):250-6. doi: 10.4103/0973-1296.153074.
Gastric cancer (GC) is one of the most frequently occurring digestive tract cancers and fewer chemotherapeutic drugs for GC have shown promising results. In this study, we investigated the anti-tumor activity of shikonin, a natural compound isolated from the Chinese plant Lithospermum erythrorhizon, against the human GC cell line HGC-27.
HGC-27 cells treated with shikonin at a concentration of 30μM or above showed significant growth inhibition compared to control cells. Shikonin-treated cells also underwent apoptosis as detected by flow cytometric analysis and microscopic examination of cellular morphology. Further investigation into the underlying mechanism of apoptosis by western blot showed that the shikonin promoted the activation of poly-(ADP-ribose)-polymerase, caspase-3 and caspase-9 following 24 h or 48 h of treatment time, as well as the activation of caspase-8, but only after 48 h of treatment time. Furthermore, the levels of mitochondrial membrane potential, B-cell lymphoma 2 (Bcl-2) and Bcl-extra large were reduced following shikonin treatment while the level of Bax was increased. In addition, shikonin also caused a significant reduction of the protein Survivin, while having little effect on the expression on X-linked inhibitor of apoptosis protein.
Taken together, these results showed that the shikonin exhibited its anti-tumor activity against HGC-27 cells through inhibiting cell growth and promoting apoptosis by targeting mitochondrial-related signaling pathway. Our finding may represent a positive step in finding a natural and effective compound that could be important implication for future development of chemotherapeutic and/or chemopreventive agent against GC.
胃癌（GC）是最常见的消化道癌症之一，用于GC的化疗药物显示出有前景结果的较少。在本研究中，我们研究了从中国植物紫草中分离出的天然化合物紫草素对人GC细胞系HGC - 27的抗肿瘤活性。
与对照细胞相比，用浓度为30μM及以上的紫草素处理的HGC - 27细胞显示出显著的生长抑制。通过流式细胞术分析和细胞形态显微镜检查检测，用紫草素处理的细胞也发生了凋亡。通过蛋白质印迹法对凋亡的潜在机制进行进一步研究表明，紫草素在处理24小时或48小时后促进了聚（ADP - 核糖）聚合酶、半胱天冬酶 - 3和半胱天冬酶 - 9的激活，以及半胱天冬酶 - 8的激活，但仅在处理48小时后。此外，紫草素处理后线粒体膜电位、B细胞淋巴瘤2（Bcl - 2）和Bcl - 超大蛋白水平降低，而Bax水平升高。此外，紫草素还导致存活蛋白的显著减少，而对凋亡蛋白X连锁抑制剂的表达影响很小。
综上所述，这些结果表明紫草素通过抑制细胞生长并靶向线粒体相关信号通路促进凋亡，从而对HGC - 27细胞发挥其抗肿瘤活性。我们的发现可能是找到一种天然有效化合物的积极一步，这对未来开发针对GC的化疗和/或化学预防剂可能具有重要意义。
