Antitumor effects of the silencing of programmed cell death ligand 1 in colorectal cancer via immunoregulation

Chen,Yilin; Huang,Ying; Lu,Xingrong; Wang,Gaoxiong; Chi,Pan

doi:10.3892/or.2018.6738

Antitumor effects of the silencing of programmed cell death ligand 1 in colorectal cancer via immunoregulation

Authors:
- Yilin Chen
- Ying Huang
- Xingrong Lu
- Gaoxiong Wang
- Pan Chi
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Affiliations: Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China, Department of Colorectal Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China, Department of General Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian 362000, P.R. China
Published online on: September 26, 2018 https://doi.org/10.3892/or.2018.6738
Pages: 3370-3380
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Activation of programmed cell death 1 (PD‑1)/PD‑ligand 1 (PD‑L1) can promote immune suppression of the tumor microenvironment. However, the effects and mechanisms of PD‑L1 silencing on colorectal cancer growth are largely unknown. In the present study, PD‑L1 expression was compared in colorectal cancer and paracancerous tissues by immunofluorescence. A stable colorectal carcinoma cell line encoding PD‑L1 short hairpin RNA (shRNA) was established. Thereafter, inoculated tumors were modeled in C57B/L6 mice. Experiments were divided into 3 groups: control group, vector group, and PD‑L1 silencing group (inoculated with the stable CT26 cell line encoding PD‑L1 shRNA). Following decapitation of the mice, tumors were weighed and apoptosis of tumor cells was detected. The number and viability of cluster of differentiation (CD)4+ and CD8+ T cells were analyzed by flow cytometry and a cell counting kit assay, respectively. Compared with paracancerous tissue, colorectal cancer tissue extensively expressed PD‑L1, RAC‑α serine/threonine‑protein kinase (AKT), and phosphatidylinositol 3‑kinase (PI3K). Lymphocyte‑activating gene 3 (LAG‑3) expression was observed at the edge of tumor tissue, but rarely observed in paracancerous tissue. A stable CT26 cell line encoding PD‑L1 shRNA was established, and lack of PD‑L1 expression was confirmed by reverse transcription‑polymerase chain reaction and western blotting. Compared with the control, the shPD‑L1 group demonstrated reduced tumor growth, a high level of apoptosis in tumor cells, a low level of PI3K and AKT expression, and an increased number of cells and greater activity of CD4+ T and CD8+ T cells. Taken together, PD‑L1 silencing promoted tumor cell apoptosis, at least in part, through the activation of CD4+ and CD8+ T cells.

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