Institute of Traslational Medicine, Medical College, Yangzhou University, Yangzhou 225001, PR China; Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou 225000, PR China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou 225001, PR China.
Institute of Traslational Medicine, Medical College, Yangzhou University, Yangzhou 225001, PR China; The Key Laboratory of Syndrome Differentiation and Treatment of Gastric Cancer of the State Administration of Traditional Chinese Medicine, Yangzhou 225001, PR China.
Biomed Pharmacother. 2018 Nov;107:738-745. doi: 10.1016/j.biopha.2018.08.049. Epub 2018 Aug 20.
As a representative traditional Chinese medicine made by modern pharmaceutical technology, Jinlong Capsule (JLC) has been used for several decades to treat liver cancer with significantly improved clinical outcomes as adjuvant therapy. JLC consists of three medicinal animals including freshly prepared Bungarus, Agkistrodon and Gecko. The active components were extracted by the process of modern cryogenic and biochemical separation from raw animals. However, the specific molecular mechanisms underlying the antitumor activities of JLC were not fully investigated. In the current study, experiments were carried out to examine the effect of JLC on anti-proliferative, pro-apoptotic activities of human gastric cancer (GC) cell lines in vivo and in vitro.
MTT assay was used to observe the viability of MGC-803 and BGC-823 cells treated with JLC. Apoptosis and cell cycle distribution of MGC-803 and BGC-823 cells induced by JLC were analyzed by flow cytometry. Western blot assay was used to detect the effect of JLC on apoptosis-related proteins, including Bax, Bcl-2, survivin and caspase-3. Transmission electron microscopy (TEM) was used to evaluate the microstructure of apoptotic GC cells. Tumor growth in vivo was monitored using live-imaging system. Immunohistochemical staining (IHC) was used to examine the expression of apoptosis-related proteins in tumor tissues.
Our data indicated that JLC inhibited proliferation and induced apoptosis of MGC-803 and BGC-823 cells in a concentration-dependent manner. JLC significantly inhibited tumor growth in nude mice. Both in vivo and in vitro studies showed that JLC could downregulate the expression of Bcl-2 and survivin, whereas upregulate the levels of bax and caspase-3. JLC had significant antitumor effects in human GC through cell cycle arresting. Besides, JLC altered the microstructure of GC cells.
These findings demonstrate that JLC can be considered as a promising candidate in GC treatment.
金龙胶囊（JLC）是一种采用现代制药技术制成的代表性中药，作为辅助治疗肝癌已有几十年的历史，临床疗效显著。JLC 由三种药用动物组成，包括新鲜制备的金环蛇、银环蛇和蛤蚧。活性成分通过现代低温生化分离技术从生药中提取。然而，JLC 抗肿瘤活性的具体分子机制尚未得到充分研究。本研究旨在探讨 JLC 对人胃癌（GC）细胞系体内和体外抗增殖、促凋亡活性的影响。
采用 MTT 法观察 JLC 处理的 MGC-803 和 BGC-823 细胞活力。流式细胞术分析 JLC 诱导 MGC-803 和 BGC-823 细胞凋亡和细胞周期分布。Western blot 法检测 JLC 对凋亡相关蛋白（包括 Bax、Bcl-2、survivin 和 caspase-3）的影响。透射电镜（TEM）评估凋亡 GC 细胞的微观结构。采用活体成像系统监测体内肿瘤生长。免疫组织化学染色（IHC）检测肿瘤组织中凋亡相关蛋白的表达。
我们的数据表明，JLC 呈浓度依赖性抑制 MGC-803 和 BGC-823 细胞的增殖并诱导其凋亡。JLC 显著抑制裸鼠肿瘤生长。体内和体外研究均表明，JLC 可下调 Bcl-2 和 survivin 的表达，而上调 bax 和 caspase-3 的水平。JLC 通过细胞周期阻滞对人 GC 具有显著的抗肿瘤作用。此外，JLC 改变了 GC 细胞的微观结构。
这些发现表明 JLC 可作为 GC 治疗的一种有前途的候选药物。
