Inhibitor of DNA-binding protein 1 knockdown arrests the growth of colorectal cancer cells and suppresses hepatic metastasis in vivo

Lai,Xiaolan; Liao,Jinrong; Lin,Wansong; Huang,Chuanzhong; Li,Jieyu; Lin,Jizhen; Chen,Qiang; Ye,Yunbin

doi:10.3892/or.2014.3172

Inhibitor of DNA-binding protein 1 knockdown arrests the growth of colorectal cancer cells and suppresses hepatic metastasis in vivo

Authors:
- Xiaolan Lai
- Jinrong Liao
- Wansong Lin
- Chuanzhong Huang
- Jieyu Li
- Jizhen Lin
- Qiang Chen
- Yunbin Ye
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Affiliations: Graduate School of Education, Fujian Medical University, Fuzhou, Fujian 350108, P.R. China, Laboratory of Immuno-Oncology, Fujian Provincial Cancer Hospital, Fuzhou, Fujian 350014, P.R. China, Department of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China
Published online on: May 8, 2014 https://doi.org/10.3892/or.2014.3172
Pages: 79-88

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Abstract

Inhibitor of DNA-binding protein 1 (ID1) is commonly abnormally overexpressed in colorectal cancer (CRC); yet, the functional significance of ID1 in the growth and invasive properties of CRC cells remains largely unclear. The present study investigated the effects of ID1 downregulation on the cell growth and metastatic features of CRC. Using lentiviral shRNA infection, stable ID1-knockdown (KD) HCT116 and SW620 cells, human metastatic CRC cell lines, were created. In vitro, the migration/invasion capacity of the ID1-KD CRC cells was assessed by a wound healing assay. The activities of MMP2 and MMP-9 were measured by gelatin zymography. The expression of CXC chemokine receptor 4 (CXCR4), PCNA and survivin were determined by immunoblot analysis and qRT-PCR. The effects of ID1 knockdown on tumor growth and hepatic metastasis were demonstrated by a xenograft study in mice. The results showed evident decreases in proliferation, migration and invasion and an increased apoptosis rate in the ID1-KD CRC cells. Similarly, ID1 knockdown significantly decreased mRNA and protein levels of PCNA, survivin, CXCR4, MMP2 and MMP9. Overexpression of CXCR4 antagonized the negative effect on the migration and invasion abilities of the ID1-KD cells. As compared with the control, ID1 knockdown prevented tumor growth and profoundly suppressed hepatic metastasis in vivo. The present study demonstrated the significance of ID1 in colon cancer progression, and its effect on tumor invasiveness and metastatic properties may be partly dependent on CXCR4.

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