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c-Met Targeting Enhances the Effect of Irradiation and Chemical Agents against Malignant Colon Cells Harboring a KRAS Mutation
Li, Yingbo1,3; Wang, Jinxi1,2; Gao, Xing1,2; Han, Weihua2; Zheng, Yongxiang1,3; Xu, Huan1; Zhang, Chuanling1,3; He, Qiuchen1,3; Zhang, Lihe1,3; Li, Zhongxin1,2; Zhou, Demin1,3
刊名PLOS ONE
2014-11-26
DOI10.1371/journal.pone.0113186
9期:11
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
资助者National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China ; National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]METASTATIC COLORECTAL-CANCER ; HEPATOCYTE GROWTH-FACTOR ; K-RAS MUTATIONS ; 1ST-LINE TREATMENT ; RNA INTERFERENCE ; GENE ; PROGRESSION ; ACTIVATION ; INHIBITOR ; CARCINOMA
英文摘要

Although EGFR-targeted therapy has been beneficial to colorectal cancer patients, several studies have showed this clinical benefit was restricted to patients with wild-type KRAS exon 2 colorectal cancer. Therefore, it is crucial to explore efficient treatment strategies in patients with KRAS mutations. c-Met is an emerging target for the development of therapeutics against colorectal cancer. In this study, we first used the SW620 cell line, which has an activating KRAS mutation, to generate a stable cell line with conditional regulation of c-Met, which is an essential gene for growth and an oncogene. Using this approach, we evaluated the benefits of combined c-Met-targeted therapy with irradiation or chemical agents. In this cell line, we observed that the proliferation and migration of SW620 cells were reduced by the induction of c-Met shRNA. Furthermore, c-Met knockdown enhanced the anti-proliferative effects of 5-FU and Taxol but not cisplatin, irinotecan or sorafenib. These enhancements were also observed in another colon cancer cells line HCT-116, which also has a KRAS mutation. The response of SW620 cells to irradiation was also enhanced by c-Met knockdown. This method and obtained data might have important implications for exploring the combinatory effects of targeted therapies with conventional medications. Moreover, the data suggested that the combination of c-Met-targeted therapy with chemotherapy or irradiation might be an effective strategy against colorectal cancer harboring a KRAS mutation.

语种英语
所属项目编号2010CB12300 ; 20932001 ; 91029711 ; 81172332 ; 81301881
资助者National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China ; National Basic Research Program of China (973 Program) ; National Natural Science Foundation of China
WOS记录号WOS:000349145400037
引用统计
被引频次:4[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51294
专题北京大学药学院
作者单位1.Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China
2.Hebei Med Univ, Hosp 4, Dept Surg 2, Shijiazhuang, Hebei, Peoples R China
3.Peking Univ, Sch Pharmaceut Sci, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Li, Yingbo,Wang, Jinxi,Gao, Xing,et al. c-Met Targeting Enhances the Effect of Irradiation and Chemical Agents against Malignant Colon Cells Harboring a KRAS Mutation[J]. PLOS ONE,2014,9(11).
APA Li, Yingbo.,Wang, Jinxi.,Gao, Xing.,Han, Weihua.,Zheng, Yongxiang.,...&Zhou, Demin.(2014).c-Met Targeting Enhances the Effect of Irradiation and Chemical Agents against Malignant Colon Cells Harboring a KRAS Mutation.PLOS ONE,9(11).
MLA Li, Yingbo,et al."c-Met Targeting Enhances the Effect of Irradiation and Chemical Agents against Malignant Colon Cells Harboring a KRAS Mutation".PLOS ONE 9.11(2014).
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