MicroRNA-21-mediated regulation of Sprouty2 protein expression enhances the cytotoxic effect of 5-fluorouracil and metformin in colon cancer cells

被引：63
作者：
Feng, Yin-Hsun [1 ,2 ,3 ]
Wu, Chao-Liang [2 ,4 ]
Shiau, Al-Li [2 ,5 ]
Lee, Jenq-Chang [6 ]
Chang, Jan-Gowth [7 ]
Lu, Pei-Jung [2 ]
Tung, Chao-Ling [1 ]
Feng, Li-Yia [8 ]
Huang, Wen-Tsung [9 ]
Tsao, Chao-Jung [9 ]
机构：
[1] Chi Mei Med Ctr, Div Hematol & Oncol, Dept Internal Med, Tainan 71004, Taiwan
[2] Natl Cheng Kung Univ, Inst Clin Med, Coll Med, Tainan 70101, Taiwan
[3] Chung Hwa Univ Med Technol, Coll Med & Life Sci, Tainan 71755, Taiwan
[4] Natl Cheng Kung Univ, Dept Biochem & Mol Biol, Coll Med, Tainan 70101, Taiwan
[5] Natl Cheng Kung Univ, Dept Microbiol & Immunol, Coll Med, Tainan 70101, Taiwan
[6] Natl Cheng Kung Univ, Dept Surg, Coll Med, Tainan 70101, Taiwan
[7] Kaohsiung Med Univ Hosp, Dept Lab Med, Kaohsiung 80708, Taiwan
[8] Natl Kaohsiung Univ Hosp & Tourism, Kaohsiung 81271, Taiwan
[9] Chi Mei Med Ctr, Dept Hematol & Oncol, Tainan 73657, Taiwan
来源：
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE | 2012年 / 29卷 / 05期
关键词：
Sprouty; microRNA-21; colon cancer; fluorouracil; metformin; BREAST-CANCER; TRANSLOCATION DOMAIN; SIGNALING PATHWAYS; KINASE; INHIBITOR; GROWTH; ACTIVATION; ANTAGONIST; DROSOPHILA; CARCINOMA;
D O I：
10.3892/ijmm.2012.910
中图分类号：
R-3 [医学研究方法]; R3 [基础医学];
学科分类号：
1001 ;
摘要：
Sprouty2 (Spry2) was identified recently as a tumor suppressor gene in cancer cells which inhibits the activation of receptor tyrosine kinases (RTKs). The present study explored the effect of Spry2 in colon cancer cells in order to assess its potential use in the treatment of colon cancer. Expression of Spry2 inhibited the growth of a colon cancer cell line, HCT 116, and induced sensitization to fluorouracil (5-FU) and metformin. Spry2 promoted apoptosis of cancer cells in association with activation of the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) pathway and the blockade of Ras-Raf-Erk signaling. Treatment of Spry2-HCT 116 cells with metformin resulted in a more prominent effect on the inhibition of cell migration. Inhibition of microRNA-21 (mir-21) induced upregulation of Spry2 and PT'EN which underscores the importance of mir-21 in Spry2-associated tumorigenesis of the colon. These results point toward a potential strategy for colon cancer treatment worthy of further investigation.
引用
收藏
页码：920 / 926
页数：7
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