CDK-associated Cullin 1 can promote cell proliferation and inhibit cisplatin-induced apoptosis in the AGS gastric cancer
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WORLD JOURNAL OF SURGICAL ONCOLOGY
RESEARCH
Open Access
CDK-associated Cullin 1 can promote cell proliferation and inhibit cisplatin-induced apoptosis in the AGS gastric cancer cell line Qi Zheng1,2, Ling-Yu Zhao3, Ying Kong1, Ke-Jun Nan1*, Yu Yao1 and Zi-Jun Liao2
Abstract Background: Gastric cancer is a common and highly lethal malignancy in the world, but its pathogenesis remains elusive. In this study, we focus on the biological functions of CDK-associated Cullin1 (CAC1), a novel gene of the cullin family, in gastric cancer, which may help us to further understand the origin of this malignancy. Methods: The AGS and MGC803 gastric cancer cell lines and the GES-1 gastric mucosa cell line were selected for study. At first, CAC1 expressions of those cell lines were examined by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blot examinations, then CAC1 small interfering RNA (CAC1-siRNA) were designed and transfected into the AGS cell line with a relatively high level of CAC1. Once CAC1 was silenced, a series of biological characteristics of AGS cells such as cell proliferation, cell cycle, apoptosis, and expressions of apoptosis-related genes (P53, BCL2 and BAX) were determined by MTT, flow cytometry, qRT-PCR and western blot, respectively. Results: CAC1 expression of AGS or MGC803 was much higher than that of GES-1. After CAC1 expression was effectively depressed by RNA interference in AGS cells, significant cell growth inhibition occurred. Furthermore, the proportion of cells treated with CAC1-siRNA increased in the G1 phase and decreased in the S phase, indicative of G1 cell cycle arrest. More importantly, the proportions of early/late apoptosis in AGS cells were enhanced with cis-diaminedichloroplatinum (cisplatin, CDDP) treatment, but to a higher extent with cisplatin plus CAC1-siRNA. Interestingly, BCL2 mRNA copies showed about a 30% decrease in the cisplatin group, but dropped by around 60% in the cisplatin plus CAC1-siRNA group. Conversely, the P53 mRNA expressions obtained nearly a two-fold increase in the cisplatin group, in addition to a five-fold increase in the cisplatin plus CAC1-siRNA group, and the BAX mRNA levels had almost a two- and four-fold augmentation, respectively. Meanwhile, P53, BAX and BCL2 showed the same alteration patterns in western blot examinations. Conclusions: CAC1 can promote cell proliferation in the AGS gastric cancer cell line. Moreover, it can prevent AGS cells from experiencing cisplatin-induced apoptosis via modulating expressions of P53, BCL2 and BAX. Keywords: Gastric cancer, CDK-associated Cullin1, Proliferation, Cell cycle, Apoptosis
Background Gastric cancer is one of the most common malignant tumors and the second leading cause of cancer death in the world, responsible for a total of 989,600 new cases and 738,000 deaths annually [1]. Over past years, there has been a steady decline in the incidence and mortality risk of gastric cancer in most countries [2], due to the tremendous * Correspondence: [email protected] 1 Depar
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