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Article

Silencing GOLPH3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways

  • Authors:
    • Zhi-Ping Zhou
    • Lin-Pei Wang
    • Zhong-Shi Hong
    • Cheng-Zhi Qiu
    • Ming-Zhen Wang
    • Zhi-Xiong Chen
    • Long-Feng Tang
    • Wai-Shi Yu
    • Chun-Xiao Wang
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China, Department of Proctology, The Fifth Hospital of Xiamen City, Xiamen, Fujian 361101, P.R. China
  • Pages: 1183-1192
    |
    Published online on: July 5, 2018
       https://doi.org/10.3892/ijo.2018.4471
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Abstract

Golgi phosphorylated protein (GOLPH)3 is overexpressed in colorectal cancer tissues and promotes the proliferation of colon cancer cells. A previous study by the authors demonstrated that GOLPH3 was associated with poor prognosis in colorectal cancer. However, the association between GOLPH3 gene overexpression and resistance to platinum-based drugs in colon cancer remains unknown. In the present study, the association between GOLPH3 overexpression and resistance of HT29 colon cancer cells to cisplatin and the mechanism underlying the development of chemoresistance were investigated. HT29 cells were divided into five groups. The expression of GOLPH3 mRNA was measured in the control and siRNA transfection groups. Reverse transcription-quantitative polymerase chain reaction analysis, cell proliferation, colony formation assay, tumor sphere formation and apoptosis (Annexin V) assays, western blotting and a nude mouse tumorigenicity assay were performed. HT29 cells were resistant to 10 µM cisplatin treatment, whereas the expression of GOLPH3, P-glycoprotein, phosphorylated extracellular signal-regulated kinase (pERK)1/2 and β-catenin protein was significantly upregulated compared with the control group. With cisplatin treatment, silencing GOLPH3 gene expression downregulated the expression of these proteins, reduced cell proliferation and tumorigenicity, induced apoptosis and reversed the resistance of HT29 cells to cisplatin. In addition, the change in pERK1/2 and β-catenin expression demonstrated that the mechanism of GOLPH3 overexpression involved in cisplatin resistance was associated with activation of the mitogen-activated protein kinase/ERK and Wnt/β‑catenin signaling pathways in HT29 cells. The tumorigenicity experiment in nude mice also demonstrated that silencing GOLPH3 expression increased the sensitivity of HT29 cells to cisplatin in vivo. Therefore, overexpression of GOLPH3 may be involved in the resistance of HT29 colon cancer cells to cisplatin chemotherapy by activating multiple cell signaling pathways.
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Copy and paste a formatted citation
Spandidos Publications style
Zhou Z, Wang L, Hong Z, Qiu C, Wang M, Chen Z, Tang L, Yu W and Wang C: Silencing GOLPH3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways. Int J Oncol 53: 1183-1192, 2018.
APA
Zhou, Z., Wang, L., Hong, Z., Qiu, C., Wang, M., Chen, Z. ... Wang, C. (2018). Silencing GOLPH3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways. International Journal of Oncology, 53, 1183-1192. https://doi.org/10.3892/ijo.2018.4471
MLA
Zhou, Z., Wang, L., Hong, Z., Qiu, C., Wang, M., Chen, Z., Tang, L., Yu, W., Wang, C."Silencing GOLPH3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways". International Journal of Oncology 53.3 (2018): 1183-1192.
Chicago
Zhou, Z., Wang, L., Hong, Z., Qiu, C., Wang, M., Chen, Z., Tang, L., Yu, W., Wang, C."Silencing GOLPH3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways". International Journal of Oncology 53, no. 3 (2018): 1183-1192. https://doi.org/10.3892/ijo.2018.4471
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou Z, Wang L, Hong Z, Qiu C, Wang M, Chen Z, Tang L, Yu W and Wang C: Silencing GOLPH3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways. Int J Oncol 53: 1183-1192, 2018.
APA
Zhou, Z., Wang, L., Hong, Z., Qiu, C., Wang, M., Chen, Z. ... Wang, C. (2018). Silencing GOLPH3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways. International Journal of Oncology, 53, 1183-1192. https://doi.org/10.3892/ijo.2018.4471
MLA
Zhou, Z., Wang, L., Hong, Z., Qiu, C., Wang, M., Chen, Z., Tang, L., Yu, W., Wang, C."Silencing GOLPH3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways". International Journal of Oncology 53.3 (2018): 1183-1192.
Chicago
Zhou, Z., Wang, L., Hong, Z., Qiu, C., Wang, M., Chen, Z., Tang, L., Yu, W., Wang, C."Silencing GOLPH3 gene expression reverses resistance to cisplatin in HT29 colon cancer cells via multiple signaling pathways". International Journal of Oncology 53, no. 3 (2018): 1183-1192. https://doi.org/10.3892/ijo.2018.4471
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