Abstract
Low expression levels of the programmed cell death 5 (PDCD5) gene have been reported in numerous human cancers, however, PDCD5 expression has not been investigated in hepatic cancer. The present study aims to investigate the biological behavior of PDCD5 overexpression in hepatocellular carcinoma (HCC) cells. The PDCD5 gene was stably transfected into the HepG2 HCC cell line (HepG2-PDCD5), and the expression levels of PDCD5 were examined by quantitative polymerase chain reaction and western blotting. An MTT assay was used to assess the cellular proliferating ability, and propidium iodide (PI) staining was used to evaluate the cell cycle by flow cytometry. The cells were incubated with 2 ng/ml transforming growth factor (TGF)-β for 7 days in order to induce invasion and epithelial-mesenchymal transition (EMT). Apoptosis was measured by Annexin V-fluorescein isothiocyanate and PI double labeling. A Boyden chamber invasion assay was carried out to detect tumor invasion. Western blotting was performed to detect the protein expression levels of PDCD5, insulin-like growth factor (IGF)-1 and the EMT marker, Snail. The results showed that the HepG2-PDCD5 cells exhibited slower proliferation rates and high G2/M cell numbers compared with those of the HepG2 and HepG2-Neo controls (P<0.05). The PDCD5 transfected cells showed higher sensitivity to cisplatin treatment than the HepG2-Neo cells, with a higher p53 protein expression level. PDCD5 overexpression can attenuate tumor invasion, EMT and the level of IGF-1 protein induced by TGF-β treatment. In conclusion, stable transfection of the PDCD5 gene can inhibit growth and induce cell cycle arrest in HepG2 cells, and its also notably improves the apoptosis-inducing effects of cisplatin, and reverses invasion and EMT induced by TGF-β. The use of PDCD5 is a novel strategy for improving the chemotherapeutic effects on HCC.
Highlights
A number of studies have demonstrated that apoptosis is closely associated with the initiation, progression and recurrence of cancer [1,2,3]
It was demonstrated that the transfection of programmed cell death 5 (PDCD5) into HepG2 cells could change the biological behaviors of tumors, such as the cellular proliferation, cell cycle progression, cisplatin sensitivity, tumor invasion and epithelial‐mesenchymal transition (EMT)
A higher percentage of HepG2‐PDCD5 cells were in the G2/M phase compared with the HepG2 and HepG2‐Neo cells
Summary
A number of studies have demonstrated that apoptosis is closely associated with the initiation, progression and recurrence of cancer [1,2,3]. It is important to manipulate apoptosis‐regulating factors in the effective treatment of cancer patients. Human programmed cell death 5 (PDCD5), formerly designated as TF‐1 cell apoptosis‐related gene 19, was cloned from TF‐1 cells during the apoptotic process induced by cytokine withdrawal. PDCD5 plays a significant role in cellular apoptosis, and its overexpression in TF‐1, MGC‐803 and HeLa cells facilitates apoptosis triggered by growth factor or serum withdrawal [4]. PDCD5 is widely expressed in various tissues and its mRNA expression level is significantly higher in adult tissues than in fetal tissues. The level of PDCD5 protein is significantly increased and is located in the nuclei preceding the externalization of phosphatidylserine and the fragmentation of chromosomal DNA [5]
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