Changes in the expression of cancer- and metastasis-related genes and proteins after metformin treatment under different metabolic conditions in endometrial cancer cells.
Endometrial cancer
Hyperglycemia
Hyperinsulinemia
Metformin
Journal
Heliyon
ISSN: 2405-8440
Titre abrégé: Heliyon
Pays: England
ID NLM: 101672560
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
30
07
2022
revised:
20
05
2023
accepted:
24
05
2023
medline:
14
6
2023
pubmed:
14
6
2023
entrez:
14
6
2023
Statut:
epublish
Résumé
Hyperinsulinemia and elevated estrogen levels are known risk factors for endometrial cancer (EC) development and are associated with obesity, type 2 diabetes mellitus (T2DM), insulin resistance, among others. Metformin, an insulin-sensitizing drug, displays anti-tumor effects in cancer patients, including EC, but the mechanism of action is still not completely understood. In the present study, the effects of metformin on gene and protein expression were investigated in pre- and postmenopausal EC After treating the cells with metformin (0.1 and 1.0 mmol/L), changes in the expression of >160 cancer- and metastasis-related gene transcripts were evaluated with RNA arrays. A total of 19 genes and 7 proteins were selected for a follow-up expression analysis, including further treatment conditions, in order to evaluate the influence of hyperinsulinemia and hyperglycemia on metformin-induced effects. Changes in the expression of BCL2L11, CDH1, CDKN1A, COL1A1, PTEN, MMP9 and TIMP2 were analyzed on gene and protein level. The consequences resulting from the detected expression changes as well as the influence of varying environmental influences are discussed in detail. With the presented data, we contribute to a better understanding of the direct anti-cancer activity of metformin as well as its underlying mechanism of action in EC cells. Although further research will be necessary to confirm the data, the influence of different environmental settings on metformin-induced effects could be highlighted with the presented data. Additionally, gene and protein regulation were not similar in the pre- and postmenopausal
Identifiants
pubmed: 37313172
doi: 10.1016/j.heliyon.2023.e16678
pii: S2405-8440(23)03885-9
pmc: PMC10258389
doi:
Types de publication
Journal Article
Langues
eng
Pagination
e16678Informations de copyright
© 2023 The Authors.
Déclaration de conflit d'intérêts
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Références
Nat Rev Cancer. 2017 Jan;17(1):38-53
pubmed: 27932800
Front Oncol. 2019 Aug 08;9:744
pubmed: 31440472
Trends Mol Med. 2017 Apr;23(4):310-319
pubmed: 28279624
Fam Cancer. 2005;4(2):187-90
pubmed: 15951972
Eur J Gynaecol Oncol. 1998;19(1):78-81
pubmed: 9476066
Endocr Rev. 1990 May;11(2):266-301
pubmed: 2114281
Front Endocrinol (Lausanne). 2021 Apr 23;12:644159
pubmed: 33967958
Theranostics. 2019 Oct 21;9(26):8294-8311
pubmed: 31754397
Gynecol Oncol. 2015 Jul;138(1):147-53
pubmed: 25913129
Oncol Lett. 2015 Dec;10(6):3457-3465
pubmed: 26788150
Tumour Biol. 2012 Aug;33(4):935-41
pubmed: 22270451
Cancer Metastasis Rev. 2015 Jun;34(2):347-57
pubmed: 26081722
Front Pharmacol. 2020 Sep 15;11:498758
pubmed: 33041786
Eur J Obstet Gynecol Reprod Biol. 2019 Jun;237:33-41
pubmed: 31009857
Oncogene. 2013 Mar 21;32(12):1475-87
pubmed: 22665053
BMC Cancer. 2018 Apr 18;18(1):438
pubmed: 29669520
World J Surg Oncol. 2020 Jul 8;18(1):161
pubmed: 32641130
Medicine (Baltimore). 2018 Jul;97(29):e10994
pubmed: 30024495
Cell Signal. 2017 Jun;34:92-101
pubmed: 28336232
J Mol Endocrinol. 2020 Apr;64(3):125-132
pubmed: 31990657
Gynecol Oncol. 2016 Feb;140(2):270-6
pubmed: 26607780
Semin Reprod Med. 2008 Nov;26(6):494-9
pubmed: 18951331
Gynecol Oncol. 2014 Jan;132(1):236-40
pubmed: 24189334
Front Endocrinol (Lausanne). 2014 May 19;5:76
pubmed: 24904527
Nature. 1970 Aug 15;227(5259):680-5
pubmed: 5432063
Nat Rev Endocrinol. 2014 Mar;10(3):143-56
pubmed: 24393785
Histopathology. 2013 Mar;62(4):632-41
pubmed: 23379820
J Hematol Oncol. 2020 Jun 3;13(1):64
pubmed: 32493414
J Cell Biochem. 2011 May;112(5):1259-67
pubmed: 21465524
Eur Rev Med Pharmacol Sci. 2019 Feb;23(4):1778-1785
pubmed: 30840303
Eur J Clin Pharmacol. 2015 Jun;71(6):691-697
pubmed: 25939711
J Exp Clin Cancer Res. 2014 May 11;33:41
pubmed: 24887156
Int J Mol Sci. 2019 Nov 04;20(21):
pubmed: 31689961
Diabetes Care. 2012 Feb;35(2):299-304
pubmed: 22266734
Hum Cell. 2002 Jun;15(2):81-95
pubmed: 12227503
Biomed Res Int. 2015;2015:920618
pubmed: 25866823
Oncogene. 2011 Oct 13;30(41):4275-88
pubmed: 21532628
PLoS One. 2013 Dec 30;8(12):e84757
pubmed: 24386413
PLoS One. 2018 Jan 31;13(1):e0191805
pubmed: 29385181
Drug Res (Stuttg). 2020 Oct;70(10):478-483
pubmed: 32791535
Rom J Morphol Embryol. 2016;57(4):1235-1240
pubmed: 28174789
Genes Cancer. 2016 Nov;7(11-12):368-382
pubmed: 28191283
Nucleic Acid Ther. 2013 Feb;23(1):29-34
pubmed: 23205572
Oncogene. 2018 Jan 18;37(3):341-351
pubmed: 28945226
Am J Pathol. 1998 Jun;152(6):1401-6
pubmed: 9626043
Cancer Cell. 2021 Jan 11;39(1):68-82.e9
pubmed: 33186519
Biochem Cell Biol. 2018 Feb;96(1):19-25
pubmed: 28482162
Mol Hum Reprod. 2004 Sep;10(9):641-50
pubmed: 15273280
Mol Cancer Ther. 2015 Feb;14(2):586-96
pubmed: 25527635
Gynecol Oncol. 2014 Feb;132(2):438-42
pubmed: 24269517
Diabetes Res Clin Pract. 1986 Apr;2(1):1-8
pubmed: 3522145
Clin Cancer Res. 2013 Jul 1;19(13):3533-44
pubmed: 23674493
Endocrinol Metab Clin North Am. 2012 Jun;41(2):335-50, vi
pubmed: 22682634
JAMA. 2019 May 21;321(19):1926-1927
pubmed: 31009043
Int J Mol Sci. 2021 Jul 31;22(15):
pubmed: 34361036
Adipocyte. 2020 Dec;9(1):415-426
pubmed: 32718202
Future Sci OA. 2019 Aug 22;5(8):FSO410
pubmed: 31534778
Gynecol Oncol. 2017 Oct;147(1):167-180
pubmed: 28760367
Arch Biochem Biophys. 2004 Jan 15;421(2):267-76
pubmed: 14984207
Int J Mol Med. 2000 Jul;6(1):47-50
pubmed: 10851265
Front Endocrinol (Lausanne). 2019 May 07;10:294
pubmed: 31133988
Sci Rep. 2021 Jun 3;11(1):11684
pubmed: 34083618
Oncol Lett. 2017 Nov;14(5):5865-5870
pubmed: 29113219
Anticancer Res. 2008 Sep-Oct;28(5A):2715-9
pubmed: 19035300
Sci Rep. 2016 Jun 28;6:28597
pubmed: 27349853
J Cell Sci. 2013 Jan 15;126(Pt 2):393-401
pubmed: 23525005
Cancer. 1995 Dec 15;76(12):2565-71
pubmed: 8625086
Sci Rep. 2019 Sep 3;9(1):12702
pubmed: 31481751
Cancer Res. 2002 Nov 1;62(21):6318-22
pubmed: 12414663
Reprod Sci. 2020 Jan;27(1):267-277
pubmed: 32046384
Crit Rev Eukaryot Gene Expr. 2016;26(1):49-62
pubmed: 27278885
Anticancer Res. 2014 Aug;34(8):4127-34
pubmed: 25075039
Biomolecules. 2019 Jan 08;9(1):
pubmed: 30626087
BMJ. 2005 Jun 4;330(7503):1304-5
pubmed: 15849206
Oncogene. 2018 Aug;37(35):4769-4780
pubmed: 29780167
Lab Invest. 2009 Aug;89(8):937-47
pubmed: 19506550
Eur J Gynaecol Oncol. 1997;18(6):484-7
pubmed: 9443016
Nihon Sanka Fujinka Gakkai Zasshi. 1985 Jul;37(7):1103-11
pubmed: 4031568
J Diabetes Investig. 2020 Nov;11(6):1420-1421
pubmed: 32428991
J Immunol. 2019 Jul 1;203(1):127-136
pubmed: 31142603
Cells. 2019 Nov 18;8(11):
pubmed: 31752117
Cancer Epidemiol Biomarkers Prev. 2009 Mar;18(3):828-36
pubmed: 19240232
J Reprod Fertil. 1999 Mar;115(2):225-32
pubmed: 10434927
Oncol Lett. 2016 Nov;12(5):3626-3632
pubmed: 27900046
Arch Biochem Biophys. 2021 Jan 15;697:108680
pubmed: 33220265
Carcinogenesis. 2006 Mar;27(3):483-90
pubmed: 16332726
Chem Biol Interact. 2015 Jun 5;234:309-19
pubmed: 25437045
Diabetes Care. 2009 Sep;32(9):1620-5
pubmed: 19564453
Oncol Lett. 2012 Jun;3(6):1221-1226
pubmed: 22783422
Mol Med Rep. 2017 Aug;16(2):1445-1450
pubmed: 29067463
J Mol Endocrinol. 2012 Mar 29;48(3):R31-43
pubmed: 22355097
Gynecol Oncol. 2019 Aug;154(2):432-440
pubmed: 31178149
J Exp Clin Cancer Res. 2016 Sep 20;35(1):148
pubmed: 27644693
Cell Cycle. 2012 Aug 1;11(15):2782-92
pubmed: 22809961
Sci Rep. 2016 Jul 11;6:29370
pubmed: 27404958
Discov Med. 2018 May;25(139):211-223
pubmed: 29906404
J Cell Sci. 2005 Oct 15;118(Pt 20):4901-12
pubmed: 16219695
Med Sci Monit. 2020 Mar 08;26:e921288
pubmed: 32146479
Cell Metab. 2010 May 5;11(5):390-401
pubmed: 20444419
PLoS One. 2021 Mar 9;16(3):e0248103
pubmed: 33690729
BMC Cancer. 2016 Jul 18;16:494
pubmed: 27431388
Oncol Lett. 2018 Aug;16(2):2030-2038
pubmed: 30008897
Cell Physiol Biochem. 2018;45(4):1631-1640
pubmed: 29486474
Med Oncol. 2012 Jun;29(2):1314-27
pubmed: 21301998
Gynecol Oncol. 2003 Jun;89(3):453-9
pubmed: 12798711
Biochim Biophys Acta. 2011 Apr;1813(4):558-63
pubmed: 21295084
Cancers (Basel). 2019 Jun 07;11(6):
pubmed: 31181620
Front Oncol. 2020 Aug 19;10:1563
pubmed: 32974191
Pharmazie. 2020 Aug 1;75(8):401-406
pubmed: 32758341
Oncotarget. 2017 Sep 23;8(55):93825-93838
pubmed: 29212192
Int J Mol Sci. 2020 Dec 20;21(24):
pubmed: 33419373
Int J Gynecol Cancer. 2016 Sep;26(7):1213-21
pubmed: 27643646
Int J Gynecol Cancer. 2004 Sep-Oct;14(5):947-56
pubmed: 15361208
Nat Med. 2017 Jul 11;23(7):804-814
pubmed: 28697184
Am J Obstet Gynecol. 1972 Dec 15;114(8):1012-9
pubmed: 4673779
Front Physiol. 2018 May 23;9:604
pubmed: 29875699
Int J Cancer. 1992 Mar 12;50(5):822-7
pubmed: 1312067
Cancers (Basel). 2020 Aug 12;12(8):
pubmed: 32806533
Asian Pac J Cancer Prev. 2019 Dec 01;20(12):3539-3545
pubmed: 31870092
Gynecol Oncol. 2012 Mar;124(3):431-6
pubmed: 22101155
Cancer Res. 2009 May 15;69(10):4545-52
pubmed: 19417140
Oncotarget. 2016 Jun 14;7(24):36407-36418
pubmed: 27172796
Biochem Biophys Res Commun. 2015 Mar 6;458(2):347-51
pubmed: 25645014
Biofactors. 2009 Mar-Apr;35(2):161-4
pubmed: 19449443
Oncotarget. 2014 Nov 30;5(22):11365-80
pubmed: 25426548
Hum Cell. 2002 Sep;15(3):104-17
pubmed: 12703541
World J Gastroenterol. 2008 Dec 21;14(47):7192-8
pubmed: 19084933
Cytokine Growth Factor Rev. 2009 Jun;20(3):233-9
pubmed: 19497778
Genes Dev. 2013 Nov 15;27(22):2473-88
pubmed: 24240237
Cancer Manag Res. 2020 Dec 14;12:12747-12758
pubmed: 33364826
Cancer Res. 1991 Dec 15;51(24):6506-9
pubmed: 1660340
Breast Cancer Res Treat. 2013 Feb;137(3):807-16
pubmed: 23292119
Nat Rev Endocrinol. 2019 Oct;15(10):569-589
pubmed: 31439934
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
Mol Immunol. 2020 Feb;118:182-190
pubmed: 31896494
Cancer Res Treat. 2017 Jul;49(3):778-789
pubmed: 27857021
BMC Cancer. 2012 Jun 21;12:262
pubmed: 22720981
Anticancer Res. 2021 Feb;41(2):821-828
pubmed: 33517287
Biomed Pharmacother. 2017 Sep;93:1-7
pubmed: 28618251