Effects of Beclin 1 overexpression on aggressive phenotypes of colon cancer cells

Zhang,Mei‑Ying; Wang,Li‑Yuan; Zhao,Shuang; Guo,Xiao‑Chong; Xu,Ying‑Qi; Zheng,Zhi‑Hong; Lu,Hang; Zheng,Hua‑Chuan

doi:10.3892/ol.2018.9817

Effects of Beclin 1 overexpression on aggressive phenotypes of colon cancer cells

Authors:
- Mei‑Ying Zhang
- Li‑Yuan Wang
- Shuang Zhao
- Xiao‑Chong Guo
- Ying‑Qi Xu
- Zhi‑Hong Zheng
- Hang Lu
- Hua‑Chuan Zheng
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Affiliations: Laboratory Animal Center, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Biochemistry and Molecular Biology, College of Basic Medicine, China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Surgery, The First Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China
Published online on: December 10, 2018 https://doi.org/10.3892/ol.2018.9817
Pages: 2441-2450

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Abstract

Beclin 1 is involved in autophagy, differentiation, apoptosis and cancer progression, and functions as a haploinsufficient tumor suppressor gene. The aim of the present study was to elucidate the function of Beclin 1 in colon cancer. A Beclin 1‑expressing plasmid was transfected into HCT‑15 and HCT‑116 cells, and the phenotypes and associated molecules were determined. Beclin 1 transfectants were subcutaneously injected into nude mice to determine tumor growth, and proliferation and apoptosis levels using Ki‑67 immunostaining and terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling (TUNEL), respectively. Beclin 1 overexpression inhibited viability as determined using a Cell Counting Kit‑8 assay, inhibited migration and invasion as determined using a wound healing assay or Transwell assay, and lamellipodia formation by filamentous actin staining, induced autophagy as determined using electron microscopy, and light chain 3B (LC‑3B) expression, and apoptosis as determined using Annexin V staining in the two cell lines (P<0.05). Beclin 1 induced G2 arrest of HCT‑15 transfectants as determined using propidium iodide staining (P<0.05), whereas HCT‑116 transfectants were arrested in G1 phase (P<0.05). The two transfectants exhibited increased expression of c‑Myc, cyclin D1, β‑catenin, insulin‑response element 1 and 78 kDa glucose‑regulated protein compared with the control and mock cells as determined using the reverse transcription‑quantitative polymerase chain reaction (P<0.05). Beclin 1 overexpression upregulated LC‑3B and cyclin‑dependent kinase 4 expression, but downregulated cyclin E expression of the cancer cell lines as determined using western blot analysis (P<0.05). Beclin 1 expression in vivo significantly suppressed the proliferation of colon cancer cells in xenograft models via inducing apoptosis by TUNEL, and inhibiting proliferation by Ki‑67 expression (P<0.05). Beclin 1 overexpression may reverse aggressive phenotypes and suppress colon cancer tumor growth, and be employed as a target molecule for gene therapy of patients with colon cancer.

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