title: Lentivirus-mediated PLCγ1 gene short-hairpin RNA suppresses tumor growth and metastasis of human gastric adenocarcinoma.
abstract: Targeted molecular therapy has gradually been a potential solution in cancer therapy. Other authors' and our previous studies have demonstrated that phosphoinositide-specific phospholipase γ (PLCγ) is involved in regulating tumor growth and metastasis. However, the molecular mechanism underlying PLCγ-dependent tumor growth and metastasis of gastric adenocarcinoma and whether PLCγ may be a potential target for tumor therapy in human gastric adenocarcinoma are not yet well determined. Here, we investigated the role of PLCγ inhibition in tumor growth and metastasis of human gastric adenocarcinoma using BGC-823 cell line and a nude mouse tumor xenograft model. The results manifested that the depletion of PLCγ1 by the transduction with lentivirus-mediated PLCγ1 gene short-hairpin RNA (shRNA) vector led to the decrease of tumor growth and metastasis of human gastric adenocarcinoma in vitro and in vivo. Furthermore, the Akt/Bad, Akt/S6, and ERK/Bad signal axes were involved in PLCγ1-mediated tumor growth and metastasis of human gastric adenocarcinoma. Therefore, the abrogation of PLCγ1 signaling by shRNA could efficaciously suppress human gastric adenocarcinoma tumor growth and metastasis, with important implication for validating PLCγ1 as a potential target for human gastric adenocarcinoma.
authors.affiliation: School of Medicine, Xiamen University, Fujian, 361102, China.
authors.forename: Bingchang
authors.initials: B
authors.lastname: Zhang
authors.affiliation: School of Medicine, Xiamen University, Fujian, 361102, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Medicine, Xiamen University, Fujian, 361102, China.
authors.forename: Lianzhi
authors.initials: L
authors.lastname: Dai
authors.affiliation: Zhongshan Hospital, Xiamen University, Fujian, 361004, China.
authors.forename: Heguo
authors.initials: H
authors.lastname: Cai
authors.affiliation: School of Medicine, Xiamen University, Fujian, 361102, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: School of Medicine, Xiamen University, Fujian, 361102, China.
authors.forename: Song
authors.initials: S
authors.lastname: Gang
authors.affiliation: School of Medicine, Xiamen University, Fujian, 361102, China.
authors.forename: Tianhui
authors.initials: T
authors.lastname: Hu
authors.affiliation: Zhongshan Hospital, Xiamen University, Fujian, 361004, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Xia
authors.affiliation: School of Medicine, Xiamen University, Fujian, 361102, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D016086:Lentivirus / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D051966:Phospholipase C gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051057:Proto-Oncogene Proteins c-akt; D051966:Phospholipase C gamma
keywords: PLCγ1; ShRNA; human gastric adenocarcinoma cells; tumor growth; tumor metastasis
references.citation: Oncogene. 2003 Aug 28;22(36):5586-91
references.pmid: 12944906
references.citation: Oncol Rep. 2015 May;33(5):2183-9
references.pmid: 25813126
references.citation: Dev Cell. 2014 Mar 31;28(6):633-46
references.pmid: 24656741
references.citation: Cancer Cell. 2013 Sep 9;24(3):347-64
references.pmid: 24029232
references.citation: Folia Histochem Cytobiol. 2014;52(3):178-86
references.pmid: 25308733
references.citation: Cancer Cell. 2007 Dec;12(6):559-71
references.pmid: 18068632
references.citation: Int J Immunopathol Pharmacol. 2015 Jun;28(2):194-200
references.pmid: 25921630
references.citation: J Cardiovasc Pharmacol. 2010 Jun;55(6):555-9
references.pmid: 20179606
references.citation: PLoS One. 2014 Mar 21;9(3):e92748
references.pmid: 24658023
references.citation: Biochem Biophys Res Commun. 2011 Oct 28;414(3):575-80
references.pmid: 21986528
references.citation: J Biol Chem. 2002 Mar 15;277(11):9335-41
references.pmid: 11744703
references.citation: Urol Oncol. 2008 Jul-Aug;26(4):386-91
references.pmid: 18367108
references.citation: Cardiovasc Diabetol. 2015 Jun 03;14:69
references.pmid: 26036798
references.citation: World J Gastroenterol. 2003 Nov;9(11):2413-8
references.pmid: 14606067
references.citation: Mol Cancer Ther. 2009 May;8(5):1305-11
references.pmid: 19417158
references.citation: Oncogene. 2007 May 10;26(21):3020-6
references.pmid: 17130835
references.citation: Genes Dev. 2003 Jun 1;17(11):1346-51
references.pmid: 12782653
references.citation: Sci Rep. 2015 May 18;5:10336
references.pmid: 25981581
references.citation: Science. 1997 Oct 24;278(5338):687-9
references.pmid: 9381178
references.citation: Cancer Res. 2008 Dec 15;68(24):10187-96
references.pmid: 19074886
references.citation: PLoS One. 2015 Apr 15;10(4):e0124007
references.pmid: 25875631
references.citation: Annu Rev Biochem. 2001;70:281-312
references.pmid: 11395409
references.citation: Nutr Cancer. 2015;67(3):523-31
references.pmid: 25837881
references.citation: J Cell Mol Med. 2015 Aug;19(8):1877-86
references.pmid: 25754021
references.citation: Nat Protoc. 2007;2(2):329-33
references.pmid: 17406593
references.citation: PLoS One. 2012;7(6):e38972
references.pmid: 22701738
references.citation: J Cell Biol. 2005 Nov 21;171(4):663-73
references.pmid: 16301332
references.citation: Anticancer Res. 2009 Dec;29(12):4965-9
references.pmid: 20044603
references.citation: Pharmacol Ther. 2014 May;142(2):164-75
references.pmid: 24333502
references.citation: Tumour Biol. 2015 Nov;36(11):8379-87
references.pmid: 26018507
references.citation: Cell. 2007 Jun 29;129(7):1261-74
references.pmid: 17604717
references.citation: J Biol Chem. 2011 Nov 4;286(44):37919-31
references.pmid: 21873429
references.citation: J Med Assoc Thai. 2010 Dec;93 Suppl 7:S311-23
references.pmid: 21294432
references.citation: Biochim Biophys Acta. 2007 May;1773(5):642-52
references.pmid: 16926057
references.citation: Int J Med Sci. 2013 May 20;10(7):870-82
references.pmid: 23781133
references.citation: Target Oncol. 2015 Sep;10 (3):393-404
references.pmid: 25341405
references.citation: Science. 1999 Nov 12;286(5443):1358-62
references.pmid: 10558990
references.citation: Carcinogenesis. 2011 Oct;32(10):1518-24
references.pmid: 21771724
references.citation: BMC Res Notes. 2012 Jul 10;5:214
references.pmid: 22554284
references.citation: J Dermatol Sci. 2015 Aug;79(2):127-36
references.pmid: 26051877
references.citation: Clin Cancer Res. 2008 Jul 1;14(13):4336-44
references.pmid: 18594017
references.citation: Biochem Pharmacol. 2014 Oct 15;91(4):522-33
references.pmid: 25150213
references.citation: Phytomedicine. 2009 Sep;16(9):887-90
references.pmid: 19303753
references.citation: J Biol Regul Homeost Agents. 2015 Apr-Jun;29(2):307-15
references.pmid: 26122218
references.citation: Clin Exp Metastasis. 2003;20(4):285-90
references.pmid: 12856715
references.citation: Adv Biol Regul. 2013 Sep;53(3):309-18
references.pmid: 23925006
references.citation: Mol Cancer Res. 2011 Oct;9(10):1418-28
references.pmid: 21840932