SPR965, a Dual PI3K/mTOR Inhibitor, as a Targeted Therapy in Ovarian Cancer.
SPR965
cell proliferation
cell stress
invasion
ovarian cancer
Journal
Frontiers in oncology
ISSN: 2234-943X
Titre abrégé: Front Oncol
Pays: Switzerland
ID NLM: 101568867
Informations de publication
Date de publication:
2020
2020
Historique:
received:
31
10
2020
accepted:
14
12
2020
entrez:
4
3
2021
pubmed:
5
3
2021
medline:
5
3
2021
Statut:
epublish
Résumé
SPR965 is an inhibitor of PI3K and mTOR C1/C2 and has demonstrated anti-tumorigenic activity in a variety of solid tumors. We sought to determine the effects of SPR965 on cell proliferation and tumor growth in human serous ovarian cancer cell lines and a transgenic mouse model of high grade serous ovarian cancer (KpB model) and identify the underlying mechanisms by which SPR965 inhibits cell and tumor growth. SPR965 showed marked anti-proliferative activity by causing cell cycle arrest and inducing cellular stress in ovarian cancer cells. Treatment with SPR965 significantly inhibited tumor growth in KpB mice, accompanied by downregulation of Ki67 and VEGF and upregulation of Bip expression in ovarian tumors. SPR965 also inhibited adhesion and invasion through induction of the epithelial-mesenchymal transition process. As expected, downregulation of phosphorylation of AKT and S6 was observed in SPR965-treated ovarian cancer cells and tumors. Our results suggest that SPR965 has significant anti-tumorigenic effects in serous ovarian cancer
Identifiants
pubmed: 33659215
doi: 10.3389/fonc.2020.624498
pmc: PMC7919852
doi:
Types de publication
Journal Article
Langues
eng
Pagination
624498Informations de copyright
Copyright © 2021 Tran, Sullivan, Chan, Yin, Sun, Fang, Dugar, Zhou and Bae-Jump.
Déclaration de conflit d'intérêts
SD is a founder of Sphaera Pharma Singapore Pte Ltd. Sphaera supplied drug for this study. L-YC is an employee of Nexcelom Bioscience LLC. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Int J Mol Sci. 2018 Nov 10;19(11):
pubmed: 30423811
Cancer Lett. 2014 Feb 1;343(1):24-32
pubmed: 24041865
Clin Cancer Res. 2019 Mar 1;25(5):1472-1478
pubmed: 30563934
Free Radic Biol Med. 2000 May 1;28(9):1387-404
pubmed: 10924858
Int J Mol Sci. 2020 Apr 18;21(8):
pubmed: 32325639
Clin Cancer Res. 2020 Aug 15;26(16):4268-4279
pubmed: 32398324
Oncologist. 2014 May;19(5):528-35
pubmed: 24718516
Cancers (Basel). 2019 Jul 05;11(7):
pubmed: 31284467
Oncotarget. 2016 Nov 15;7(46):74820-74833
pubmed: 27533079
Invest New Drugs. 2019 Jun;37(3):424-430
pubmed: 30056610
J Clin Oncol. 2012 Jun 10;30(17):2039-45
pubmed: 22529265
Gynecol Oncol. 2011 Oct;123(1):19-26
pubmed: 21752435
Int J Mol Sci. 2019 Sep 05;20(18):
pubmed: 31491919
Onco Targets Ther. 2019 Sep 17;12:7637-7647
pubmed: 31571914
Drugs Today (Barc). 2007 Oct;43(10):659-69
pubmed: 17987219
Clin Cancer Res. 2011 Aug 15;17(16):5322-32
pubmed: 21712451
Oncotarget. 2017 Dec 06;8(69):113874-113884
pubmed: 29371953
BMC Cancer. 2015 Nov 11;15:894
pubmed: 26560145
Cancer Lett. 2014 Jun 28;348(1-2):38-49
pubmed: 24650799
Eur J Pharmacol. 2014 Apr 15;729:45-53
pubmed: 24561043
CA Cancer J Clin. 2020 Jan;70(1):7-30
pubmed: 31912902
BMC Cancer. 2019 Jun 24;19(1):618
pubmed: 31234823
Life Sci. 2020 Aug 15;255:117481
pubmed: 32135183
Oncogene. 2007 Mar 22;26(13):1932-40
pubmed: 17001314
Apoptosis. 2004 Nov;9(6):667-76
pubmed: 15505410
Gynecol Oncol. 2019 Apr;153(1):135-148
pubmed: 30686552
Anticancer Drugs. 2017 Jun;28(5):503-513
pubmed: 28240679
Mol Cancer Ther. 2015 Aug;14(8):1916-27
pubmed: 26013318
Science. 2004 Apr 23;304(5670):554
pubmed: 15016963
Clin Cancer Res. 2015 Feb 15;21(4):730-8
pubmed: 25500057
Chin J Cancer. 2015 Jan;34(1):4-16
pubmed: 25556614
Cancer Res. 2012 Aug 15;72(16):4141-53
pubmed: 22617326
Semin Cancer Biol. 2019 Dec;59:147-160
pubmed: 31128298
Gynecol Oncol. 2016 Mar;140(3):450-6
pubmed: 26731724
Eur J Med Chem. 2019 Dec 1;183:111718
pubmed: 31581005
J Hematol Oncol. 2009 Oct 27;2:45
pubmed: 19860903
J Nucl Med. 2015 Dec;56(12):1828-35
pubmed: 26429956
J Clin Oncol. 2003 Sep 1;21(17):3194-200
pubmed: 12860964
Cell Oncol (Dordr). 2020 Aug;43(4):669-680
pubmed: 32382996
Cancer Cell. 2005 Jun;7(6):561-73
pubmed: 15950905
Cell Oncol (Dordr). 2018 Aug;41(4):409-426
pubmed: 29790111
Lancet Oncol. 2014 Jul;15(8):852-61
pubmed: 24882434
Oncotarget. 2014 May 15;5(9):2372-89
pubmed: 24796583
Nat Rev Cancer. 2020 Feb;20(2):74-88
pubmed: 31686003
Gynecol Oncol. 2012 Jul;126(1):47-53
pubmed: 22487539
Oncotarget. 2016 Jun 28;7(26):39582-39594
pubmed: 27074576
Med Oncol. 2019 Nov 12;37(1):4
pubmed: 31713081
Gynecol Oncol. 2015 Apr;137(1):173-9
pubmed: 25677064
Expert Opin Investig Drugs. 2019 Nov;28(11):977-988
pubmed: 31594388