Targeted silencing of TRPM7 ion channel induces replicative senescence and produces enhanced cytotoxicity with gemcitabine in pancreatic adenocarcinoma.
作者： Nelson S. Yee , Weiqiang Zhou , Minsun Lee , Rosemary K. Yee
DOI: 10.1016/J.CANLET.2011.12.007
关键词: Small interfering RNA 、 Cell aging 、 Gemcitabine 、 Biology 、 Cancer research 、 TRPM7 、 Senescence 、 Pancreatic cancer 、 Molecular biology 、 Gene silencing 、 RNA interference
摘要: The transient receptor potential TRPM7 ion channel is required for cellular proliferation in pancreatic epithelia and adenocarcinoma. To elucidate the mechanism that mediates function of TRPM7, we examined its role survival cancer cells. RNA interference-mediated silencing did not induce apoptotic cell death. TRPM7-deficient cells underwent replicative senescence with up-regulation p16(CDKN2A) WRN mRNA. combination anti-TRPM7 siRNA gemcitabine produced enhanced cytotoxicity as compared to alone. Thus, preventing senescence, modulation expression may help improve treatment response by combining apoptosis-inducing agents.
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sci-hub.se 参考文章(44)
V’yacheslav Lehen’kyi, Natalia Prevarskaya, Oncogenic TRP channels. Advances in Experimental Medicine and Biology. ,vol. 704, pp. 929- 945 ,(2011) , 10.1007/978-94-007-0265-3_48
Hagop Kantarjian, Michael J. Keating, William Plunkett, James Abbruzzese, Peter Tarassoff, Ralf Grunewald, Pharmacologically directed design of the dose rate and schedule of 2',2'-difluorodeoxycytidine (Gemcitabine) administration in leukemia. Cancer Research. ,vol. 50, pp. 6823- 6826 ,(1990)
Monica J. S. Nadler, Meredith C. Hermosura, Kazunori Inabe, Anne-Laure Perraud, Qiqin Zhu, Alexander J. Stokes, Tomohiro Kurosaki, Jean-Pierre Kinet, Reinhold Penner, Andrew M. Scharenberg, Andrea Fleig, LTRPC7 is a Mg·ATP-regulated divalent cation channel required for cell viability Nature. ,vol. 411, pp. 590- 595 ,(2001) , 10.1038/35079092
Rebecca Siegel, Elizabeth Ward, Otis Brawley, Ahmedin Jemal, Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA: A Cancer Journal for Clinicians. ,vol. 61, pp. 212- 236 ,(2011) , 10.3322/CAAC.20121
Silvia Ferrè, Andrzej Mazur, Jeanette A M Maier, Low-magnesium induces senescent features in cultured human endothelial cells Magnesium Research. ,vol. 20, pp. 66- 71 ,(2007) , 10.1684/MRH.2007.0093
J L Abbruzzese, R Grunewald, E A Weeks, D Gravel, T Adams, B Nowak, S Mineishi, P Tarassoff, W Satterlee, M N Raber, A phase I clinical, plasma, and cellular pharmacology study of gemcitabine. Journal of Clinical Oncology. ,vol. 9, pp. 491- 498 ,(1991) , 10.1200/JCO.1991.9.3.491
Federica I. Wolf, Valentina Trapani, Cell (patho)physiology of magnesium Clinical Science. ,vol. 114, pp. 27- 35 ,(2008) , 10.1042/CS20070129
Kristopher Clark, Michiel Langeslag, Bart van Leeuwen, Leonie Ran, Alexey G Ryazanov, Carl G Figdor, Wouter H Moolenaar, Kees Jalink, Frank N van Leeuwen, TRPM7, a novel regulator of actomyosin contractility and cell adhesion The EMBO Journal. ,vol. 25, pp. 290- 301 ,(2006) , 10.1038/SJ.EMBOJ.7600931
Stephen G. Chun, Nelson S. Yee, Werner syndrome as a hereditary risk factor for exocrine pancreatic cancer: Potential role of WRN in pancreatic tumorigenesis and patient-tailored therapy Cancer Biology & Therapy. ,vol. 10, pp. 430- 437 ,(2010) , 10.4161/CBT.10.5.12763
Xin Shi, Shengli Liu, Jörg Kleeff, Helmut Friess, Markus W. Büchler, Acquired resistance of pancreatic cancer cells towards 5-Fluorouracil and gemcitabine is associated with altered expression of apoptosis-regulating genes. Oncology. ,vol. 62, pp. 354- 362 ,(2002) , 10.1159/000065068