Carbon ion irradiation-induced DNA damage evokes cell cycle arrest and apoptosis via the pRb/E2F1/c-Myc signaling pathway in p53-deficient prostate cancer PC-3 cells

Carbon ion radiotherapy has the advantages of better therapeutic effect and fewer side effects compared with those of X-rays in many kinds of tumors,including prostate cancer,and thus is an attractive treatment approach for prostate cancer.However,the biological effects and underlying mechanisms of carbon ion irradiation in prostate cancer are not yet fully understood.Therefore,this study systematically compared the effects of carbon ion irradiation with those of X-ray irradiation on DNA damage response and found that carbon ion irradiation was more effective than X-ray irradiation.Carbon ion irradiation can induce a high level of DNA double-strand break damage,reflected by the number of y-H2 A histone family member X foci,as well as by the foci lasting time and size.Moreover,carbon ion irradiation exhibited strong and long-lasting inhibitory effect on cell survival capability,induced prolonged cell cycle arrest,and increased apoptosis in PC-3 cells.As an underlying mechanism,we speculated that carbon ion irradiation-induced DNA damage evokes cell cycle arrest and apoptosis via the pRb/E2 F1/c-Myc signaling pathway to enhance the radiosensitivity of p53-deficient prostate cancer PC-3 cells.Collectively,the present study suggests that carbon ion irradiation is more efficient than X-ray irradiation and may help to understand the effects of different radiation qualities on the survival potential of p53-deficient prostate cancer cells.

Integrative analysis of the inverse expression patterns in pancreas development and cancer progression

BACKGROUND As the malignant tumor,pancreatic cancer with a meager 5-years survival rate has been widely concerning.However,the molecular mechanisms that result in malignant transformation of pancreatic cells remain elusive.AIM To investigate the gene expression profiles in normal or malignant transformed pancreas development.METHODS MaSigPro and ANOVA were performed on two pancreas development datasets downloaded from the Gene Expression Omnibus database.Six pancreatic cancer datasets collected from TCGA database were used to establish differentially expressed genes related to pancreas development and pancreatic cancer.Moreover,gene clusters with highly similar interpretation patterns between pancreas development and pancreatic cancer progression were established by self-organizing map and singular value decomposition.Additionally,the hypergeometric test was performed to compare the corresponding interpretation patterns.Abnormal regions of metabolic pathway were analyzed using the Subpathway-GM method.RESULTS This study established the continuously upregulated and downregulated genes at different stages in pancreas development and progression of pancreatic cancer.Through analysis of the differentially expressed genes,we established the inverse and consistent direction development-cancer pattern associations.Based on the application of the Subpathway-GM analysis,we established 17 significant metabolic sub-pathways that were closely associated with pancreatic cancer.Of note,the most significant metabolites sub-pathway was related to glycerophospholipid metabolism.CONCLUSION The inverse and consistent direction development-cancer pattern associations were established.There was a significant correlation in the inverse patterns,but not consistent direction patterns.