人脐带华通氏胶干细胞（hWJSC）提取物通过诱导细胞周期停滞和凋亡来抑制卵巢癌细胞系OVCAR3和SKOV3。
Human Wharton's Jelly Stem Cell (hWJSC) Extracts Inhibit Ovarian Cancer Cell Lines OVCAR3 and SKOV3 by Inducing Cell Cycle Arrest and Apoptosis.
作者信息
Kalamegam Gauthaman, Sait Khalid Hussein Wali, Ahmed Farid, Kadam Roaa, Pushparaj Peter Natesan, Anfinan Nisreen, Rasool Mahmood, Jamal Mohammad Sarwar, Abu-Elmagd Muhammed, Al-Qahtani Mohammed
机构信息
Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia.
Faculty of Medicine, Asian Institute of Medicine, Science and Technology (AIMST) University, Bedong, Malaysia.
出版信息
Front Oncol. 2018 Dec 7;8:592. doi: 10.3389/fonc.2018.00592. eCollection 2018.
Ovarian cancer is a highly lethal and the second highest in mortality among gynecological cancers. Stem cells either naïve or engineered are reported to inhibit various human cancers in both and . Herein we report the cancer inhibitory properties of human Wharton's jelly stem cell (hWJSC) extracts, namely its conditioned medium (hWJSC-CM) and cell lysate (hWJSC-CL) against two ovarian cancer cell lines (OVCAR3 and SKOV3) . Cell metabolic activity assay of OVCAR3 and SKOV3 cells treated with hWJSC-CM (12.5, 25, 50, 75, 100%) and hWJSC-CL (5, 10, 15, 30, and 50 μg/ml) demonstrated concentration dependent inhibition at 24-72 h. Morphological analysis of OVCAR3 and SKOV3 cells treated with hWJSC-CM (50, 75, 100%) and hWJSC-CL (15, 30, and 50 μg/ml) for 24-72 h showed cell shrinkage, membrane damage/blebbings and cell death. Cell cycle assay demonstrated an increase in the sub-G1 and G2M phases of cell cycle following treatment with hWJSC-CM (50, 75, 100%) and hWJSC-CL (10, 15, and 30 μg/ml) at 48 h. Both OVCAR3 and SKOV3 cells demonstrated mild positive expression of activated caspase 3 following treatment with hWJSC-CM (50%) and hWJSC-CL (15 μg/ml) for 24 h. Cell migration of OVCAR3 and SKOV3 cells were inhibited following treatment with hWJSC-CM (50%) and hWJSC-CL (15 μg/ml) for 48 h. Tumor spheres (TS) of OVCAR3 and SKOV3 treated with hWJSC-CM (50, 75, 100%) and hWJSC-CL (10, 15, 30 μg/ml) for 48 h showed altered surface changes including vacuolations and reduction in size of TS. TS of OVCAR3 and SKOV3 also showed the presence of few ovarian cancer stem cells (CSCs) in minimal numbers following treatment with hWJSC-CM (50%) or hWJSC-CL (15 μg/ml) for 48 h. Real-time gene expression analysis of OVCAR3 and SKOV3 treated with hWJSC-CM (50%) or hWJSC-CL (15 μg/ml) for 48 h demonstrated decreased expression of cell cycle regulatory genes (cyclin A2, Cyclin E1), prostaglandin receptor signaling genes (EP2, EP4) and the pro-inflmmatory genes (IL-6, TNF-α) compared to untreated controls. The results indicate that hWJSC-CM and hWJSC-CL inhibit ovarian cancer cells at mild to moderate levels by inducing cellular changes, cell cycle arrest, apoptosis, decreasing the expression of CSC markers and related genes regulation. Therefore, the stem cell factors in hWJSCs extracts can be useful in cancer management.
卵巢癌是一种高度致命的癌症，在妇科癌症中死亡率排名第二。据报道，天然或经过改造的干细胞在体内和体外均能抑制多种人类癌症。在此，我们报告了人脐带华通氏胶干细胞（hWJSC）提取物，即其条件培养基（hWJSC-CM）和细胞裂解物（hWJSC-CL）对两种卵巢癌细胞系（OVCAR3和SKOV3）的癌症抑制特性。用hWJSC-CM（12.5%、25%、50%、75%、100%）和hWJSC-CL（5μg/ml、10μg/ml、15μg/ml、30μg/ml和50μg/ml）处理OVCAR3和SKOV3细胞后的细胞代谢活性测定表明，在24至72小时内呈浓度依赖性抑制。用hWJSC-CM（50%、75%、100%）和hWJSC-CL（15μg/ml、30μg/ml和50μg/ml）处理OVCAR3和SKOV3细胞24至72小时后的形态学分析显示细胞皱缩、膜损伤/起泡和细胞死亡。细胞周期分析表明，在48小时时，用hWJSC-CM（50%、75%、10０%）和hWJSC-CL（10μg/ml、15μg/ml和30μg/ml）处理后，细胞周期的亚G1期和G2M期增加。用hWJSC-CM（50%）和hWJSC-CL（15μg/ml）处理24小时后，OVCAR3和SKOV3细胞均显示活化的半胱天冬酶3轻度阳性表达。用hWJSC-CM（50%）和hWJSC-CL（15μg/ml）处理48小时后，OVCAR3和SKOV3细胞的迁移受到抑制。用hWJSC-CM（50%、75%、100%）和hWJSC-CL（10μg/ml、15μg/ml、30μg/ml）处理48小时后的OVCAR3和SKOV3肿瘤球（TS）显示表面变化改变，包括空泡化和TS大小减小。用hWJSC-CM（50%）或hWJSC-CL（15μg/ml）处理48小时后的OVCAR3和SKOV3的TS也显示存在少量卵巢癌干细胞（CSC）。用hWJSC-CM（50%）或hWJSC-CL（15μg/ml）处理48小时后的OVCAR3和SKOV3的实时基因表达分析表明，与未处理的对照相比，细胞周期调节基因（细胞周期蛋白A2、细胞周期蛋白E1）、前列腺素受体信号基因（EP2、EP4）和促炎基因（IL-6、TNF-α）的表达降低。结果表明，hWJSC-CM和hWJSC-CL通过诱导细胞变化、细胞周期停滞、凋亡、降低CSC标志物的表达和相关基因调节来轻度至中度抑制卵巢癌细胞。因此，hWJSCs提取物中的干细胞因子可用于癌症治疗。
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