| Title | c-Met Targeting Enhances the Effect of Irradiation and Chemical Agents against Malignant Colon Cells Harboring a KRAS Mutation |
| Authors | Li, Yingbo Wang, Jinxi Gao, Xing Han, Weihua Zheng, Yongxiang Xu, Huan Zhang, Chuanling He, Qiuchen Zhang, Lihe Li, Zhongxin Zhou, Demin |
| Affiliation | Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China. Hebei Med Univ, Hosp 4, Dept Surg 2, Shijiazhuang, Hebei, Peoples R China. Peking Univ, Sch Pharmaceut Sci, Beijing 100871, Peoples R China. |
| Keywords | METASTATIC COLORECTAL-CANCER HEPATOCYTE GROWTH-FACTOR K-RAS MUTATIONS 1ST-LINE TREATMENT RNA INTERFERENCE GENE PROGRESSION ACTIVATION INHIBITOR CARCINOMA |
| Issue Date | 2014 |
| Publisher | plos one |
| Citation | PLOS ONE.2014,9,(11). |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/156280 |
| ISSN | 1932-6203 |
| DOI | 10.1371/journal.pone.0113186 |
| Indexed | SCI(E) PubMed |
| Appears in Collections: | 天然药物与仿生药物国家重点实验室 药学院 |
