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Effects of siRNA-mediated HDAC2 gene silence on proliferation and apoptosis of human pancreatic cell line |
YAN Yan, ZHANG You-li, XU Min |
(Department of Gastroenterology, the Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212001, China) |
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Abstract [Abstract] Objective: To investigate the effects of siRNA-mediated histone deacetylase 2(HDAC2) gene silence on the proliferation and apoptosis of human pancreatic cell line PaTu8988. Methods: Human pancreatic cancer cell line PaTu8988 cells were cultured and divided into five groups: control group, 20 nmol/L negative siRNA group, 40 nmol/L negative siRNA group, 20 nmol/L HDAC2 siRNA group, and 40 nmol/L HDAC2 siRNA group. Transient transfection of small interfering RNA (siRNA) against HDAC2 on human pancreatic cancer cell line PaTu8988 cells were performed by Lipofectamine 2000. Expression of HDAC2 gene was detected by quantitative real-time PCR and western blotting, respectively. The cell proliferation was determined by MTT assay. Flow cytometry was used to examine the cells apoptosis. Results: Compared with control group and negative siRNA groups, HDAC2 siRNA groups had markedly lower levels of HDAC2 expressions and lower cell growth rate, but higher cell apoptosis rate(P<0.05 or P<0.01). Conclusion: Transfection of HDAC2 siRNA could effectively inhibit the expression of HDAC2 in PaTu8988 cell lines, which suppressed the proliferation and induced apotosis of PaTu8988 cells.
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Received: 01 March 2013
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[1]Mahlknecht U, Hoelzer D. Histone acetylation modifiers in the pathogenesis of malignant disease[J]. Mol Med, 2000, 6(8):623-644.[2]Bracker TU, Sommer A, Fichtner I, et al. Efficacy of MS-275, a selective inhibitor of class Ι histone deacetylases, in human colon cancer models[J]. Int J Oncol, 2009, 35(4):909-920.[3]Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010[J]. CA Cancer J Clin, 2010, 60(5):277-300.[4]Li D, Xie K, Wolff R, et al. Pancreatic cancer[J]. Lancet, 2004, 363 (9414):1049-1057.[5]Campbell PJ, Yachida S, Mudie LJ, et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer[J]. Nature, 2010, 467(7319):1109-1113.[6]Witt O, Deubzer HE, Milde T, et al. HDAC family: What are the cancer relevant targets?[J]. Cancer Lett, 2009, 277(1):8-21.[7]Zhu P, Martin E, Menqwasser J, et al. Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis[J].Cancer Cell, 2004, 5(5):455-463.[8]Fritsche P, Seidler B, Schüler S, et al. HDAC2 mediates therapeutic resistance of pancreatic cancer cells via the BH3-only protein NOXA[J].Gut, 2009, 58(10): 1399-1409.[9]Karaqiannis TC, EIOsta A. RNA interference and potential therapeutic applications of short interfering RNAs[J]. Cancer Gene Ther, 2005, 12(10):787-795.[10]Glaser KB, Staver MJ, Waring JF, et al. Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors:defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines[J]. Mol Cancer Ther, 2003, 2(2):151-163.[11]Richon VM, Emiliani S, Verdin E, et al. A class of hybrid polar inducers of transformed cell differentiation inhibits histone deacetylases[J]. Proc Natl Acad Sci U S A, 1998, 95(6):3003-3007.[12]Furumai R, Komatsu Y, Nishino N, et al. Potent histone deacetylase inhibitors built from trichostatin A and cyclic tetrapeptide antibiotics including trapoxin[J]. Proc Natl Acad Sci U S A, 2001, 98(1):87-92. |
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