Proteomic Analyses of Gastric Cancer Cells Treated with Vesicular Stomatitis Virus Matrix Protein
Proteomic Analyses of Gastric Cancer Cells Treated with Vesicular Stomatitis Virus Matrix Protein
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水泡性口炎病毒基质蛋白治疗胃癌细胞的蛋白质组学分析
DOI：
10.1007/s10930-011-9331-3
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Canhua Huang
中科院分区：
文献类型：
--
作者：
Dequan Zeng;Tao Zhang;Shengtao Zhou;Hao Hu;Jingyi Li;Kai Huang;Yunlong Lei;Kui Wang;Yong Zhao;Rui Liu;Qiu Li;Yanjun Wen;Canhua Huang
胃癌是全球第二大致死原因，也是第四大常见癌症。虽然化疗仍然是可切除和进展期胃癌的主要治疗方法，但大多数胃癌对抗癌药物具有天然抗药性，因此迫切需要新的治疗途径。水泡性口炎病毒(VSV)能在多种类型的肿瘤细胞中优先复制，最终诱导宿主细胞的凋亡。水疱性口炎病毒基质蛋白(MP)在其作用中起主要作用。本研究证明MP的表达能有效抑制胃癌MKN28细胞的增殖和诱导细胞死亡。此外，我们利用蛋白质组学策略来表征MP处理的MKN28株和未处理的MKN28株之间的蛋白质组变化。共有97个点被鉴定为差异表达，其中62个蛋白质上调，35个蛋白质下调。功能分析揭示了三个显著修改的基因产物亚群：糖酵解酶、活性氧相关蛋白和调节RNA运输和成熟的蛋白质。用半定量RT-PCR或/和Western blotting进一步验证三种改变蛋白的表达。此外，我们还证明了MP的表达可以诱导MKN28细胞内ROS的快速积累。这些结果为MP的抗癌作用提供了证据，并提出了一种新的MP介导的细胞凋亡信号通路。我们的发现被认为是朝着更好地理解MP诱导的抗癌作用的机制迈出的重要一步。
Gastric cancer constitutes the second leading cause of mortality worldwide and the fourth most common cancer. While chemotherapy remains the primary treatment for both resectable and advanced gastric cancer, most gastric cancers are naturally resistant to anticancer drugs, rendering new therapeutic avenues in dire need. Vesicular stomatitis virus (VSV) was proved to preferentially replicate in many types of tumor cells and eventually induce apoptosis of host cells. The vesicular stomatitis virus matrix protein (MP) plays a major role in its effects. This study proved that expression of MP could effectively inhibit proliferation and induce cell death in gastric carcinoma MKN28 cells. Furthermore, we utilized a proteomics strategy to characterize proteome-wide alterations between MP-treated MKN28 lines and their untreated counterparts. A total of 97 spots were positively identified as differentially expressed, and of these 62 proteins were up-regulated, whereas 35 proteins were down-regulated. Functional analysis unraveled three significantly modified gene product subgroups: glycolytic enzymes, reactive oxygen species-associated proteins and the proteins regulating RNA transport and maturation. Expression of three altered proteins was further validated by semi-quantitative RT–PCR or/and western blotting. Furthermore, we demonstrated that MP expression could induce rapid intracellular ROS accumulation in MKN28 cells. These results provide evidence for the anti-cancer potential of MP, and a novel MP-mediated apoptotic signaling pathway is proposed. Our findings are considered a significant step toward a better understanding the mechanism of MP-induced anti-cancer effect.
影响因子：
7.4
作者：
Circu, Magdalena L.;Aw, Tak Yee
通讯作者：
Aw, Tak Yee
影响因子：
--
作者：
Narayanan, NK;Narayanan, BA;Nixon, DW
通讯作者：
Nixon, DW
影响因子：
3.7
作者：
Ahmed, M;Cramer, SD;Lyles, DS
通讯作者：
Lyles, DS