Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine

CORC > 厦门大学 > 海洋环境－已发表论文

	Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine
	Xu, Dapeng ; Cobb, Michael G. ; Gavilano, Lily ; Witherspoon, Sam M. ; Williams, Daniel ; White, Catherine D. ; Taverna, Pietro ; Bednarski, Brian K. ; Kim, Hong Jin ; Baldwin, Albert S. ; Baines, Antonio T. ; Xu DP(徐大鹏)
刊名	http://dx.doi.org/10.4161/cbt.24343
	2013
关键词	BAD-MEDIATED APOPTOSIS CONFERS RESISTANCE EXPRESSION DRUG ADENOCARCINOMA PROTOONCOGENE ACTIVATION CARCINOMA TARGET IDENTIFICATION
英文摘要	NIH [CA137845, CA92077]; Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a 5-year survival rate of only 6%. Although the cytosine analog gemcitabine is the drug commonly used to treat PDAC, chemoresistance unfortunately renders the drug ineffective. Thus, strategies that can decrease this resistance will be essential for improving the dismal outcome of patients suffering from this disease. We previously observed that oncogenic Pim-1 kinase was aberrantly expressed in PDAC tissues and cell lines and was responsible for radioresistance. Furthermore, members of the Pim family have been shown to reduce the efficacy of chemotherapeutic drugs in cancer. Therefore, we attempted to evaluate the role of Pim-3 in chemoresistance of PDAC cells. We were able to confirm upregulation of the Pim-3 oncogene in PDAC tissues and cell lines vs. normal samples. Biological consequences of inhibiting Pim-3 expression with shRNA-mediated suppression included decreases in anchorage-dependent growth, invasion through Matrigel and chemoresistance to gemcitabine as measured by caspase-3 activity. Additionally, we were able to demonstrate that Pim-1 and Pim-3 play overlapping but non-identical roles as it relates to gemcitabine sensitivity of pancreatic cancer cells. To further support the role of Pim-3 suppression in sensitizing PDAC cells to gemcitabine, we used the pharmacological Pim kinase inhibitor SGI-1776. Treatment of PDAC cells with SGI-1776 resulted in decreased phosphorylation of the proapoptotic protein Bad and cell cycle changes. When SGI-1776 was combined with gemcitabine, there was a greater decrease in cell viability in the PDAC cells vs. cells treated with either of the drugs separately. These results suggest combining drug therapies that inhibit Pim kinases, such as Pim-3, with chemotherapeutic agents, to aid in decreasing chemoresistance in pancreatic cancer.
语种	英语
出版者	LANDES BIOSCIENCE
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/88012]
专题	海洋环境－已发表论文
推荐引用方式 GB/T 7714	Xu, Dapeng,Cobb, Michael G.,Gavilano, Lily,et al. Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine[J]. http://dx.doi.org/10.4161/cbt.24343,2013.
APA	Xu, Dapeng.,Cobb, Michael G..,Gavilano, Lily.,Witherspoon, Sam M..,Williams, Daniel.,...&徐大鹏.(2013).Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine.http://dx.doi.org/10.4161/cbt.24343.
MLA	Xu, Dapeng,et al."Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine".http://dx.doi.org/10.4161/cbt.24343 (2013).