Effect of lentiviral vector-packaged interleukin-18 gene on the malignant behavior of lung cancer

Xiangqi Chen; Rui Feng; Donglan Xiong; Sheng Yang; Tingyan Lin

doi:10.3892/etm.2019.8204

Effect of lentiviral vector-packaged interleukin-18 gene on the malignant behavior of lung cancer

Exp Ther Med. 2020 Jan;19(1):319-326. doi: 10.3892/etm.2019.8204. Epub 2019 Nov 15.

Authors

Xiangqi Chen^{1

2}, Rui Feng³, Donglan Xiong¹, Sheng Yang^{3

4

5

6}, Tingyan Lin^{1

2}

Affiliations

¹ Teaching and Research Department of Respiratory Medicine, Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
² Department of Respiratory Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
³ Department of Oncology Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian 350001, P.R. China.
⁴ Teaching and Research Department of Oncology Medicine, Union Clinical Medical College of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
⁵ Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, Fujian 350001, P.R. China.
⁶ Fujian Medical University Stem Cell Research Institute, Fuzhou, Fujian 350001, P.R. China.

Abstract

Interleukin-18 (IL-18) is a multifunctional cytokine that exhibits antitumor, anti-infection and immunoregulatory functions. This study aimed to investigate the effects of lentiviral vector-packaged interleukin (IL)-18 gene on the malignant behavior of lung cancer and the potential underlying molecular mechanism of IL-18 anticancer activity. Human lung adenocarcinoma A549 cells transfected with human IL-18 gene-containing lentiviral expression vector were the IL-18 intervention group (group A), cells transfected with the empty lentiviral expression vector were empty vector group (group B), and cells without any intervention were the blank control group (group C). Reverse transcription-quantitative PCR and western blotting were used to determine IL-18 mRNA and protein expression levels. Cell Counting Kit-8, colony-formation, flow cytometry, invasion and wound-healing assays were used to evaluate the malignant behavior of A549 cells transfected with the IL-18 lentiviral vector. The expression levels of the T helper (Th)1 cell cytokine interferon-γ (IFN-γ) and the Th2 cell cytokine IL-4 were tested by ELISA, and western blotting was used to test the expressing of nuclear factor κB (NF-κB). The results demonstrated that IL-18 mRNA and protein expression levels in group A were significantly increased compared with groups B and C; the expression levels of IFN-γ in group A were higher and the expression levels of IL-4 in group A were lower compared with those in groups B and C; and the expression of NF-κB was increased in the cytoplasm and decreased in the nucleus in group A compared with groups B and C. The data indicated that, compared with the control groups, the IL-18 gene lentiviral expression vector increased the expression of IL-18, diminished A549 cell proliferative ability, enhanced apoptosis, decreased the invasive and metastatic capacities of the cells, promoted the secretion of IFN-γ, decreased the production of IL-4, reversed the imbalance of Th1/Th2 cell subsets and inhibited the nuclear activation of NF-κB, which collectively present an anti-lung cancer mechanism and deserve further study.

Keywords: biological behavior; interleukin-18 gene; lentivirus; lung cancer; molecular mechanism.