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

Feng,Yin-Hsun; Wu,Chao-Liang; Shiau,Ai-Li; Lee,Jenq-Chang; Chang,Jan-Gowth; Lu,Pei-Jung; Tung,Chao-Ling; Feng,Li-Yia; Huang,Wen-Tsung; Tsao,Chao-Jung

doi:10.3892/ijmm.2012.910

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

Authors:
- Yin-Hsun Feng
- Chao-Liang Wu
- Ai-Li Shiau
- Jenq-Chang Lee
- Jan-Gowth Chang
- Pei-Jung Lu
- Chao-Ling Tung
- Li-Yia Feng
- Wen-Tsung Huang
- Chao-Jung Tsao
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Affiliations: Division of Hematology and Oncology, Department of Internal Medicine, Chi-Mei Medical Center, Yong Kang, Tainan 71004, Taiwan, R.O.C., Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C., Department of Surgery, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan, R.O.C., Department of Laboratory Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan, R.O.C., National Kaohsiung University of Hospitality and Tourism, Kaohsiung 81271, Taiwan, R.O.C., Department of Hematology and Oncology, Chi-Mei Medical Center, Liou Ying, Tainan 73657, Taiwan, R.O.C.
Published online on: February 9, 2012 https://doi.org/10.3892/ijmm.2012.910
Pages: 920-926

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Abstract

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, HCT116, 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-HCT116 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 PTEN 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.