TY - JOUR
T1 - Transcriptomic analysis of pancreatic cancer cells in response to metformin and aspirin
T2 - An implication of synergy
AU - Yue, Wen
AU - Wang, Tao
AU - Zachariah, Emmanuel
AU - Lin, Yong
AU - Yang, Chung S.
AU - Xu, Qing
AU - DiPaola, Robert S.
AU - Tan, Xiang Lin
N1 - Funding Information:
This work was supported by Rutgers Robert Wood Johnson Foundation research funds and the Functional Genomics Core Shared Resource of the Rutgers Cancer Institute of New Jersey (P30CA072720) and a grant (Grant No. 81470132) from the National Natural Science Foundation of China. We also thank RUCDR for the RNA sequencing.
PY - 2015/8/21
Y1 - 2015/8/21
N2 - Metformin and aspirin have been studied extensively as cancer preventative and therapeutic agents. However, the underlying molecular mechanisms for the inhibitory effects of pancreatic cancer development remain undefined. To gain further insight into their biological function in pancreatic cancer, we conducted a transcriptomic analysis using RNA sequencing to assess the differential gene expression induced by metformin (5 mM) and aspirin (2 mM), alone or in combination, after treatment of PANC-1 cells for 48 hours. Compared to an untreated control, metformin down-regulated 58 genes and up-regulated 91 genes, aspirin down-regulated 12 genes only, while metformin plus aspirin down-regulated 656 genes and up-regulated 449 genes (fold-change > 2, P < 10-5). Of the top 10 genes (fold-change > 10, P < 10-10) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated ≥20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated ≥10-fold. Ingenuity Pathway Analysis (IPA) revealed that the pathways, "cholesterol biosynthesis", "cell cycle: G1/S checkpoint regulation", and "axonal guidance signaling" were the most statistically significant pathways modulated by metformin plus aspirin. Although the results need further functional validation, these data provide the first evidence for the synergistic action between metformin and aspirin in modulating the transcriptional profile of pancreatic cancer cells.
AB - Metformin and aspirin have been studied extensively as cancer preventative and therapeutic agents. However, the underlying molecular mechanisms for the inhibitory effects of pancreatic cancer development remain undefined. To gain further insight into their biological function in pancreatic cancer, we conducted a transcriptomic analysis using RNA sequencing to assess the differential gene expression induced by metformin (5 mM) and aspirin (2 mM), alone or in combination, after treatment of PANC-1 cells for 48 hours. Compared to an untreated control, metformin down-regulated 58 genes and up-regulated 91 genes, aspirin down-regulated 12 genes only, while metformin plus aspirin down-regulated 656 genes and up-regulated 449 genes (fold-change > 2, P < 10-5). Of the top 10 genes (fold-change > 10, P < 10-10) regulated by metformin plus aspirin, PCDH18, CCL2, RASL11A, FAM111B and BMP5 were down-regulated ≥20-fold, while NGFR, NPTX1, C7orf57, MRPL23AS1 and UNC5B were up-regulated ≥10-fold. Ingenuity Pathway Analysis (IPA) revealed that the pathways, "cholesterol biosynthesis", "cell cycle: G1/S checkpoint regulation", and "axonal guidance signaling" were the most statistically significant pathways modulated by metformin plus aspirin. Although the results need further functional validation, these data provide the first evidence for the synergistic action between metformin and aspirin in modulating the transcriptional profile of pancreatic cancer cells.
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U2 - 10.1038/srep13390
DO - 10.1038/srep13390
M3 - Article
C2 - 26294325
AN - SCOPUS:84939825859
SN - 2045-2322
VL - 5
JO - Scientific reports
JF - Scientific reports
M1 - 13390
ER -
