Lin Chien-Chung, Chao Pei-Yu, Shen Chia-Yao, Shu Jyuan-Jen, Yen Shiow-Kang, Huang Chih-Yang, Liu Jer-Yuh
Department of Materials Science and Engineering, National Chung Hsing University, Taichung, Taiwan , Orthopaedic Department, Armed Forces General Hospital, Taichung, Taiwan.
Am J Chin Med. 2014;42(3):743-67. doi: 10.1142/S0192415X14500487.
Osteosarcoma (OS) is a type of bone cancer. Eighty percent of this tumor will metastasize to the lungs or liver, and as a result, patients generally need chemotherapy to improve survival possibility. Recently, antitumor activity has been reported in Ocimum gratissimum aqueous extract (OGE), which has been the focus of recent extensive studies on therapeutic strategies due to its antioxidant properties. We performed pharmacogenomics analyses for the effect of OGE on human osteosarcoma U2-OS and HOS cell growth. Cell viability, Western blot and flow cytometry analysis were performed before performing pharmacogenomics analyses for the effect of OGE on human osteosarcoma U2-OS and HOS cell growth, including cDNA microarray and RT-PCR assays. Cell viability assays revealed that OGE significantly and dose-dependently decreased the viability of U2-OS and HOS cells. Increases in cell shrinkage, Sub-G1 fragments and the activation of caspase 3 indicated that OGE induced cell apoptosis in U2-OS and HOS cells. There was no change in human osteoblast hFOS cells. cDNA microarray assay demonstrated that the expression of cell cycle regulators, apoptosis-related factors and cell proliferation markers were all modified by OGE treatment. RT-PCR analysis also confirmed the down-regulation of SKA2 and BUB1B, and the up-regulation of PPP1R15A, SQSTM1, HSPA1B, and DDIT4 by OGE treatment. The finding of anticancer activity in OGE and the identification of some potential target genes raise the expectation that OGE may become a useful therapeutic drug for human OS.
骨肉瘤（OS）是一种骨癌。这种肿瘤的80%会转移至肺部或肝脏，因此，患者通常需要化疗以提高生存几率。最近，已报道了罗勒水提取物（OGE）的抗肿瘤活性，由于其抗氧化特性，它已成为近期治疗策略广泛研究的焦点。我们对OGE对人骨肉瘤U2-OS和HOS细胞生长的影响进行了药物基因组学分析。在对OGE对人骨肉瘤U2-OS和HOS细胞生长的影响进行药物基因组学分析之前，进行了细胞活力、蛋白质印迹和流式细胞术分析，包括cDNA微阵列和逆转录-聚合酶链反应（RT-PCR）检测。细胞活力检测显示，OGE显著且呈剂量依赖性地降低了U2-OS和HOS细胞的活力。细胞皱缩、亚G1期片段增加以及半胱天冬酶3的激活表明，OGE诱导U2-OS和HOS细胞凋亡。人成骨细胞hFOS细胞无变化。cDNA微阵列检测表明，细胞周期调节因子、凋亡相关因子和细胞增殖标志物的表达均因OGE处理而改变。RT-PCR分析也证实，OGE处理后，SKA2和BUB1B下调，而PPP1R15A、SQSTM1、HSPA1B和DDIT4上调。OGE中抗癌活性的发现以及一些潜在靶基因的鉴定，让人期望OGE可能成为治疗人类骨肉瘤的一种有用药物。
