title: PDCD5 transfection increases cisplatin sensitivity and decreases invasion in hepatic cancer cells.
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.
authors.affiliation: Department of Gastroenterology, Shandong Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, P.R. China.
authors.forename: Gui-Ling
authors.initials: GL
authors.lastname: Fan
authors.affiliation: Department of General Surgery, The First People's Hospital of Shanxian County, Heze, Shandong 274300, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Dentistry, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250001, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Yao
authors.affiliation: Department of Nursing, The First People's Hospital of Shanxian County, Heze, Shandong 274300, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
keywords: PDCD5; apoptosis; cisplatin; epithelial-mesenchymal transition; hepatocellular carcinoma; p53