Metformin suppresses breast cancer growth via inhibition of cyclooxygenase‑2
- Authors:
- Bin Shi
- Xinyu Hu
- Huimin He
- Wenzheng Fang
-
Affiliations: Department of Medical Oncology, Fuzhou General Hospital of Fujian Medical University, East Hospital Affiliated to Xiamen University (The 900th Hospital of The Joint Logistics Support Force of The Chinese PLA), Dongfang Hospital, Xiamen University, Fuzhou, Fujian 350025, P.R. China - Published online on: June 23, 2021 https://doi.org/10.3892/ol.2021.12876
- Article Number: 615
-
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
This article is mentioned in:
Abstract
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI | |
American Cancer Society, . Breast Cancer Facts and Figures, 2007–2008, May 2009. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2007-2008.pdfMay 21–2021 | |
Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI | |
Miller ME, Muhsen S, Olcese C, Patil S, Morrow M and Van Zee KJ: Contralateral breast cancer risk in women with ductal carcinoma in situ: Is it high enough to justify bilateral mastectomy. Ann Surg Oncol. 24:2889–2897. 2017. View Article : Google Scholar : PubMed/NCBI | |
Gandini S, Guerrieri-Gonzaga A, Puntoni M and Decensi A: Metformin and breast cancer risk. J Clin Oncol. 31:973–974. 2013. View Article : Google Scholar : PubMed/NCBI | |
Ahmadieh H and Azar ST: Type 2 diabetes mellitus, oral diabetic medications, insulin therapy, and overall breast cancer risk. ISRN Endocrinol. 2013:1812402013. View Article : Google Scholar : PubMed/NCBI | |
Brower V: Illuminating the diabetes-cancer link. J Natl Cancer Inst. 104:1048–1050. 2012. View Article : Google Scholar : PubMed/NCBI | |
Suh S and Kim KW: Diabetes and cancer: Is diabetes causally related to cancer. Diabetes Metab J. 35:193–198. 2011. View Article : Google Scholar : PubMed/NCBI | |
Scheen AJ, Beck E, De Flines J and Rorive M: Obesity, insulin resistance and type 2 diabetes: Risk factors for breast cancer. Rev Med Liege. 66:238–244. 2011.(In French). PubMed/NCBI | |
Pandey A, Forte V, Abdallah M, Alickaj A, Mahmud S, Asad S and McFarlane SI: Diabetes mellitus and the risk of cancer. Minerva Endocrinol. 36:187–209. 2011.PubMed/NCBI | |
Vigneri P, Frasca F, Sciacca L, Pandini G and Vigneri R: Diabetes and cancer. Endocr Relat Cancer. 16:1103–1123. 2009. View Article : Google Scholar : PubMed/NCBI | |
Chen TW, Liang YN, Feng D, Tao LY, Qi K, Zhang HY, Wang HX, Lin QS and Kong H: Metformin inhibits proliferation and promotes apoptosis of HER2 positive breast cancer cells by downregulating HSP90. J BUON. 18:51–56. 2013.PubMed/NCBI | |
Col NF, Ochs L, Springmann V, Aragaki AK and Chlebowski RT: Metformin and breast cancer risk: A meta-analysis and critical literature review. Breast Cancer Res Treat. 135:639–646. 2012. View Article : Google Scholar : PubMed/NCBI | |
Jalving M, Gietema JA, Lefrandt JD, de Jong S, Reyners AK, Gans RO and de Vries EG: Metformin: Taking away the candy for cancer. Eur J Cancer. 46:2369–2380. 2010. View Article : Google Scholar : PubMed/NCBI | |
Bodmer M, Meier C, Krähenbühl S, Jick SS and Meier CR: Long-term metformin use is associated with decreased risk of breast cancer. Diabetes Care. 33:1304–1308. 2010. View Article : Google Scholar : PubMed/NCBI | |
Liu B, Fan Z, Edgerton SM, Deng XS, Alimova IN, Lind SE and Thor AD: Metformin induces unique biological and molecular responses in triple negative breast cancer cells. Cell Cycle. 8:2031–2040. 2009. View Article : Google Scholar : PubMed/NCBI | |
Alimova IN, Liu B, Fan Z, Edgerton SM, Dillon T, Lind SE and Thor AD: Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro. Cell Cycle. 8:909–915. 2009. View Article : Google Scholar : PubMed/NCBI | |
Song CW, Lee H, Dings RP, Williams B, Powers J, Santos TD, Choi BH and Park HJ: Metformin kills and radiosensitizes cancer cells and preferentially kills cancer stem cells. Sci Rep. 2:3622012. View Article : Google Scholar : PubMed/NCBI | |
Soga M, Ohashi A, Taniguchi M, Matsui T and Tsuda T: The di-peptide Trp-His activates AMP-activated protein kinase and enhances glucose uptake independently of insulin in L6 myotubes. FEBS Open Bio. 4:898–904. 2014. View Article : Google Scholar : PubMed/NCBI | |
Zhuang Y and Miskimins WK: Cell cycle arrest in Metformin treated breast cancer cells involves activation of AMPK, downregulation of cyclin D1, and requires p27Kip1 or p21Cip1. J Mol Signal. 3:182008. View Article : Google Scholar : PubMed/NCBI | |
Hadad SM, Fleming S and Thompson AM: Targeting AMPK: A new therapeutic opportunity in breast cancer. Crit Rev Oncol Hematol. 67:1–7. 2008. View Article : Google Scholar : PubMed/NCBI | |
Zong M, Fan DD, Lin S, Song YP, Wang ZY, Ma XL, Qiu WH, Bai YH, Li L and Li S: Anti-cancer activity and potential mechanism of a novel aspirin derivative. Eur J Pharmacol. 791:137–146. 2016. View Article : Google Scholar : PubMed/NCBI | |
Aban M, Siddqui I, Saboor M, Pervez S and Moatter T: Haplotypes of SNPs associated with COX-2 and their comparison with histopathological features of breast cancer patients. J Immuno Ther Cancer. 3:92015. View Article : Google Scholar | |
Dhakal HP, Naume B, Synnestvedt M, Borgen E, Kaaresen R, Schlichting E, Wiedswang G, Bassarova A, Holm R, Giercksky KE and Nesland JM: Expression of cyclooxygenase-2 in invasive breast carcinomas and its prognostic impact. Histol Histopathol. 27:1315–1325. 2012.PubMed/NCBI | |
Holmes MD, Chen WY, Schnitt SJ, Collins L, Colditz GA, Hankinson SE and Tamimi RM: COX-2 expression predicts worse breast cancer prognosis and does not modify the association with aspirin. Breast Cancer Res Treat. 130:657–662. 2011. View Article : Google Scholar : PubMed/NCBI | |
Çiriş IM, Bozkurt KK, Başpinar S and Kapucuoğlu FN: Immunohistochemical COX-2 overexpression correlates with HER-2/neu overexpression in invasive breast carcinomas: A pilot study. Pathol Res Pract. 207:182–187. 2011. View Article : Google Scholar | |
Kim HS, Moon HG, Han W, Yom CK, Kim WH, Kim JH and Noh DY: COX2 overexpression is a prognostic marker for Stage III breast cancer. Breast Cancer Res Treat. 132:51–59. 2012. View Article : Google Scholar : PubMed/NCBI | |
Daneau G, Boidot R, Martinive P and Feron O: Identification of cyclooxygenase-2 as a major actor of the transcriptomic adaptation of endothelial and tumor cells to cyclic hypoxia: Effect on angiogenesis and metastases. Clin Cancer Res. 16:410–419. 2010. View Article : Google Scholar : PubMed/NCBI | |
Lyons TR, Borges VF, Betts CB, Guo Q, Kapoor P, Martinson HA, Jindal S and Schedin P: Cyclooxygenase-2-dependent lymphangiogenesis promotes nodal metastasis of postpartum breast cancer. J Clin Invest. 124:3901–3912. 2014. View Article : Google Scholar : PubMed/NCBI | |
Killian PH, Kronski E, Michalik KM, Barbieri O, Astigiano S, Sommerhoff CP, Pfeffer U, Nerlich AG and Bachmeier BE: Curcumin inhibits prostate cancer metastasis in vivo by targeting the inflammatory cytokines CXCL1 and −2. Carcinogenesis. 33:2507–2519. 2012. View Article : Google Scholar : PubMed/NCBI | |
Karavitis J, Hix LM, Shi YH, Schultz RF, Khazaie K and Zhang M: Regulation of COX2 expression in mouse mammary tumor cells controls bone metastasis and PGE2-induction of regulatory T cell migration. PLoS One. 7:e463422012. View Article : Google Scholar : PubMed/NCBI | |
Lucci A, Krishnamurthy S, Singh B, Bedrosian I, Meric-Bernstam F, Reuben J, Broglio K, Mosalpuria K, Lodhi A, Vincent L and Cristofanilli M: Cyclooxygenase-2 expression in primary breast cancers predicts dissemination of cancer cells to the bone marrow. Breast Cancer Res Treat. 117:61–68. 2009. View Article : Google Scholar : PubMed/NCBI | |
Visscher DW, Pankratz VS, Santisteban M, Reynolds C, Ristimäki A, Vierkant RA, Lingle WL, Frost MH and Hartmann LC: Association between cyclooxygenase-2 expression in atypical hyperplasia and risk of breast cancer. J Natl Cancer Inst. 100:421–427. 2008. View Article : Google Scholar : PubMed/NCBI | |
Thun MJ, Henley SJ and Patrono C: Nonsteroidal anti-inflammatory drugs as anticancer agents: Mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst. 94:252–266. 2002. View Article : Google Scholar : PubMed/NCBI | |
Luchetti CG, Mikó E, Szekeres-Bartho J, Paz DA and Motta AB: Dehydroepiandrosterone and metformin modulate progesterone-induced blocking factor (PIBF), cyclooxygenase 2 (COX2) and cytokines in early pregnant mice. J Steroid Biochem Mol Biol. 111:200–207. 2008. View Article : Google Scholar : PubMed/NCBI | |
Elia E, Sander V, Luchetti CG, Solano ME, Di Girolamo G, Gonzalez C and Motta AB: The mechanisms involved in the action of metformin in regulating ovarian function in hyperandrogenized mice. Mol Hum Reprod. 12:475–481. 2006. View Article : Google Scholar : PubMed/NCBI | |
Sobin LH and Compton CC: TNM seventh edition: What's new, what's changed: Communication from the international union against cancer and the American Joint Committee on Cancer. Cancer. 116:5336–5339. 2010. View Article : Google Scholar : PubMed/NCBI | |
Sabit H, Abdel-Ghany SE, M Said OA, Mostafa MA and El-Zawahry M: Metformin reshapes the methylation profile in breast and colorectal cancer cells. Asian Pac J Cancer Prev. 19:2991–2999. 2018.PubMed/NCBI | |
Yue W, Zheng X, Lin Y, Yang CS, Xu Q, Carpizo D, Huang H, DiPaola RS and Tan XL: Metformin combined with aspirin significantly inhibit pancreatic cancer cell growth in vitro and in vivo by suppressing anti-apoptotic proteins Mcl-1 and Bcl-2. Oncotarget. 6:21208–21224. 2015. View Article : Google Scholar : PubMed/NCBI | |
Hodges V, Tucci M and Benghuzzi H: The effects of metformin and EGCG on PANC-1 cell survival. Biomed Sci Instrum. 51:393–399. 2015.PubMed/NCBI | |
Liu K, Wang G, Ding H, Chen Y, Yu G and Wang J: Downregulation of metastasis suppressor 1(MTSS1) is associated with nodal metastasis and poor outcome in Chinese patients with gastric cancer. BMC Cancer. 10:4282010. View Article : Google Scholar : PubMed/NCBI | |
Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI | |
Pollak M: Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer. 8:915–928. 2008. View Article : Google Scholar : PubMed/NCBI | |
Hwang JT, Ha J, Park IJ, Lee SK, Baik HW, Kim YM and Park OJ: Apoptotic effect of EGCG in HT-29 colon cancer cells via AMPK signal pathway. Cancer Lett. 247:115–121. 2007. View Article : Google Scholar : PubMed/NCBI | |
Zakikhani M, Dowling R, Fantus IG, Sonenberg N and Pollak M: Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 66:10269–10273. 2006. View Article : Google Scholar : PubMed/NCBI | |
Morgensztern D and McLeod HL: PI3K/Akt/mTOR pathway as a target for cancer therapy. Anticancer Drugs. 16:797–803. 2005. View Article : Google Scholar : PubMed/NCBI | |
Okubo K, Isono M, Asano T and Sato A: Metformin augments Panobinostat's Anti-bladder cancer activity by activating AMP-activated protein kinase. Transl Oncol. 12:669–682. 2019. View Article : Google Scholar : PubMed/NCBI | |
Lipscombe LL, Goodwin PJ, Zinman B, McLaughlin JR and Hux JE: Diabetes mellitus and breast cancer: A retrospective population-based cohort study. Breast Cancer Res Treat. 98:349–356. 2006. View Article : Google Scholar : PubMed/NCBI | |
Dowling RJ, Niraula S, Stambolic V and Goodwin PJ: Metformin in cancer: Translational challenges. J Mol Endocrinol. 48:R31–R43. 2012. View Article : Google Scholar : PubMed/NCBI | |
Chen X, Li C, He T, Mao J, Li C, Lyu J and Meng QH: Metformin inhibits prostate cancer cell proliferation, migration, and tumor growth through upregulation of PEDF expression. Cancer Biol Ther. 17:507–514. 2016. View Article : Google Scholar : PubMed/NCBI | |
Cantrell LA, Zhou C, Mendivil A, Malloy KM, Gehrig PA and Bae-Jump VL: Metformin is a potent inhibitor of endometrial cancer cell proliferation-implications for a novel treatment strategy. Gynecol Oncol. 116:92–98. 2010. View Article : Google Scholar : PubMed/NCBI | |
Iglesias DA, Yates MS, van der Hoeven D, Rodkey TL, Zhang Q, Co NN, Burzawa J, Chigurupati S, Celestino J, Bowser J, et al: Another surprise from Metformin: Novel mechanism of action via K-Ras influences endometrial cancer response to therapy. Mol Cancer Ther. 12:2847–2856. 2013. View Article : Google Scholar : PubMed/NCBI | |
Sarfstein R, Friedman Y, Attias-Geva Z, Fishman A, Bruchim I and Werner H: Metformin downregulates the insulin/IGF-I signaling pathway and inhibits different uterine serous carcinoma (USC) cells proliferation and migration in p53-dependent or -independent manners. PLoS One. 8:e615372013. View Article : Google Scholar : PubMed/NCBI | |
Zhou Y, Xu JN, Zeng C, Li X, Zhou YF, Qi Y and Xue Q: Metformin suppresses prostaglandin E2-induced cytochrome P450 aromatase gene expression and activity via stimulation of AMP-activated protein kinase in human endometriotic stromal cells. Reprod Sci. 22:1162–1170. 2015. View Article : Google Scholar : PubMed/NCBI | |
Bansal K, Narayana Y and Balaji KN: Inhibition of TNF-alpha-induced cyclooxygenase-2 expression by Mycobacterium bovis BCG in human alveolar epithelial A549 cells. Scand J Immunol. 69:11–19. 2009. View Article : Google Scholar : PubMed/NCBI | |
Zidar N, Odar K, Glavac D, Jerse M, Zupanc T and Stajer D: Cyclooxygenase in normal human tissues-is COX-1 really a constitutive isoform, and COX-2 an inducible isoform. J Cell Mol Med. 13:3753–3763. 2009. View Article : Google Scholar : PubMed/NCBI | |
Rodrigues S, Bruyneel E, Rodrigue CM, Shahin E and Gespach C: Cyclooxygenase 2 and carcinogenesis. Bull Cancer. 91:Spec No: S61-S76, 2004 (In French). | |
Jørgensen SB, Jensen TE and Richter EA: Role of AMPK in skeletal muscle gene adaptation in relation to exercise. Appl Physiol Nutr Metab. 32:904–911. 2007. View Article : Google Scholar | |
Röckl KS, Witczak CA and Goodyear LJ: Signaling mechanisms in skeletal muscle: Acute responses and chronic adaptations to exercise. IUBMB Life. 60:145–153. 2008. View Article : Google Scholar | |
Huang SP, Wu MS, Shun CT, Wang HP, Hsieh CY, Kuo ML and Lin JT: Cyclooxygenase-2 increases hypoxia-inducible factor-1 and vascular endothelial growth factor to promote angiogenesis in gastric carcinoma. J Biomed Sci. 12:229–241. 2005. View Article : Google Scholar : PubMed/NCBI | |
Cianchi F, Cortesini C, Bechi P, Fantappiè O, Messerini L, Vannacci A, Sardi I, Baroni G, Boddi V, Mazzanti R and Masini E: Up-regulation of cyclooxygenase 2 gene expression correlates with tumor angiogenesis in human colorectal cancer. Gastroenterology. 121:1339–1347. 2001. View Article : Google Scholar : PubMed/NCBI | |
Hadad SM, Baker L, Quinlan PR, Robertson KE, Bray SE, Thomson G, Kellock D, Jordan LB, Purdie CA, Hardie DG, et al: Histological evaluation of AMPK signalling in primary breast cancer. BMC Cancer. 9:3072009. View Article : Google Scholar : PubMed/NCBI | |
Zhang T, Wang X, He D, Jin X and Guo P: Metformin sensitizes human bladder cancer cells to TRAIL-induced apoptosis through mTOR/S6K1-mediated downregulation of c-FLIP. Anticancer Drugs. 25:887–897. 2014. View Article : Google Scholar : PubMed/NCBI | |
Takabatake M, Daino K, Imaoka T, Nishimura M, Morioka T, Fukushi M and Shimada Y: Aberrant expression and phosphorylation of 4E-BP1, a main target of mTOR signaling, in rat mammary carcinomas: an association with etiology. In Vivo. 25:853–860. 2011.PubMed/NCBI | |
Coleman LJ, Peter MB, Teall TJ, Brannan RA, Hanby AM, Honarpisheh H, Shaaban AM, Smith L, Speirs V, Verghese ET, et al: Combined analysis of eIF4E and 4E-binding protein expression predicts breast cancer survival and estimates eIF4E activity. Br J Cancer. 100:1393–1399. 2009. View Article : Google Scholar : PubMed/NCBI | |
Akcakanat A, Sahin A, Shaye AN, Velasco MA and Meric-Bernstam F: Comparison of Akt/mTOR signaling in primary breast tumors and matched distant metastases. Cancer. 112:2352–2358. 2008. View Article : Google Scholar : PubMed/NCBI | |
Bort A, Quesada S, Ramos-Torres Á, Gargantilla M, Priego EM, Raynal S, Lepifre F, Gasalla JM, Rodriguez-Henche N, Castro A and Díaz-Laviada I: Identification of a novel 2-oxindole fluorinated derivative as in vivo antitumor agent for prostate cancer acting via AMPK activation. Sci Rep. 8:43702018. View Article : Google Scholar : PubMed/NCBI | |
Rehman G, Shehzad A, Khan AL and Hamayun M: Role of AMP-activated protein kinase in cancer therapy. Arch Pharm (Weinheim). 347:457–468. 2014. View Article : Google Scholar : PubMed/NCBI | |
Lee MS, Han HJ, Han SY, Kim IY, Chae S, Lee CS, Kim SE, Yoon SG, Park JW, Kim JH, et al: Loss of the E3 ubiquitin ligase MKRN1 represses diet-induced metabolic syndrome through AMPK activation. Nat Commun. 9:34042018. View Article : Google Scholar : PubMed/NCBI | |
Janzen NR, Whitfield J and Hoffman NJ: Interactive roles for AMPK and glycogen from cellular energy sensing to exercise metabolism. Int J Mol Sci. 19:33442018. View Article : Google Scholar : PubMed/NCBI | |
Jiralerspong S, Palla SL, Giordano SH, Meric-Bernstam F, Liedtke C, Barnett CM, Hsu L, Hung MC, Hortobagyi GN and Gonzalez-Angulo AM: Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer. J Clin Oncol. 27:3297–3302. 2009. View Article : Google Scholar : PubMed/NCBI |