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Antiproliferative effects of cetuximab on triple negative breast cancer cell line MDA-MB-231

Year 2020, , 706 - 711, 30.09.2020
https://doi.org/10.17776/csj.751778

Abstract

In this study, antiproliferative effects of the anti-EGFR monoclonal antibody Cetuximab were evaluated using MDA-MB-231 cell line originated from triple negative breast cancer. As cell kinetic parameters, we evaluated Cell index, mitotic index, labeling index and apoptotic index. For this purpose, 20 μM, 45 μM and 60 μM Cetuximab concentrations were applied to the cells using the real-time cell analysis system (xCelligence DP) and IC50 values were determined. IC50 concentrations were used for all other parameters. According to experimental results, Cetuximab administration inhibited cell kinetics of MDA-MB-231 cells. xCelligence DP instrument detected IC50 concentrations of Cetuximab for cell line. These values were 45 μM for MDA-MB-231 cells. When these IC50 value applied to cells, significant decrease was detected in mitotic index, labelling index and significant increase was detected in apoptotic index for experimental groups. Student’s t tests for paired samples were used to assign statistical significance. p<0.05 level of significance was accepted. According to the results obtained, Cetuximab has the potential to slow down the prognosis of the triple negative breast cancer subtype.

Supporting Institution

Scientific Research Project Coordination Unit of Istanbul University

Project Number

FBA-2017-24288

References

  • Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res, 13(2007), 4429-34.
  • Criscitiello C, Azim HA, Schouten PC, Linn SC, Sotiriou C. Understanding the biology of triple-negative breast cancer, Annals of Oncology, 23 (2012), vi13-vi18.
  • Buettner R, Mora LB, Jove R. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res, 8 (2002), 945-54.
  • Hamid O. Emerging treatments in oncology: focus on tyrosine kinase (erbB) receptor inhibitors. J Am Pharm Assoc, 44 (2004), 52-8.
  • Galizia G, Lieto E, De Vita F, Orditura M, Castellano P, Troiani T et al. Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer. Oncogene, 26 (2007), 3654-60.
  • Martinelli E, De Palma R, Orditura M, De Vita F, Ciardiello F. Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy. Clin Exp Immunol, 158 (2009), 1-9.
  • Koukourakis MI, Tsoutsou PG, Karpouzis A, Tsiarkatsi M, Karapantzos I, Daniilidis V et al. Radiochemotherapy with cetuximab, cisplatin, and amifostine for locally advanced head and neck cancer: a feasibility study. Int J Radiat Oncol Biol Phys, 77 (2010), 9-15.
  • Muthu M, Cheriyan VT, Rishi AK. CARP-1 / CCAR1: A biphasic regulator of cancer cell growth and apoptosis. Oncotarget, 6 (2015), 6499-6510.
  • Van de Rijn M, Perou CM, Tibshirani R, Haas P, Kallioniemi O, Kononen J et al. Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol, 161 (2002), 1991-1996.
  • Shin BK, Lee Y, Lee JB, Kim HK, Lee JB, Cho SJ et al. Breast carcinomas expressing basal markers have poor clinical outcome regardless of estrogen receptor status. Oncol Rep, 19 (2008), 617-625.
  • Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA, 98 (2001), 10869-10874.
  • Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA, 100 (2003), 8418-8423.
  • Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, Jazaeri A et al. Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA, 100 (2003), 10393-10398.
  • Banerjee S, Reis‐Filho JS, Ashley S, Steele D, Ashworth A, Lakhani SR et al. Basal-like breast carcinomas: clinical outcome and response to chemotherapy. J Clin Pathol, 59 (2006), 729-735.
  • Lehmann BD, Pietenpol JA, Tan AR. Triple-negative breast cancer: molecular subtypes and new targets for therapy. Am Soc Clin Oncol Educ Book, 35 (2015), e31-e39.
  • Uhm JE, Park YH, Yi SY, Cho EY, Choi YL, Lee SJ et al. Treatment outcomes and clinicopathologic characteristics of triple-negative breast cancer patients who received platinum-containing chemotherapy. Int J Cancer, 124 (2009), 1457-1462.
  • Baselga J, Arteaga CL. Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol, 23 (2005), 2445–59.
  • Viale G, Rotmensz N, Maisonneuve P, Bottiglieri L, Montagna E, Luini A et al. Invasive ductal carcinoma of the breast with the “triple-negative” phenotype: prognostic implications of EGFR immunoreactivity. Breast Cancer Res Treat, 116 (2009), 317-328.
  • Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res, 10 (2004), 5367-5374.
  • Kim MJ, Ro JY, Ahn SH, Kim HH, Kim SB, Gong G. Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/ neu-overexpressing phenotypes. Hum Pathol 37 (2006), 1217-1226.
  • Liu H, Fan Q, Zhang Z, Yu H, Meng F. Basal-HER2 phenotype shows poorer survival than basal-like phenotype in hormone receptor-negative invasive breast cancers. Hum Pathol, 39 (2008), 167-174.
  • Shien T, Tashiro T, Omatsu M, Masuda T, Furuta K, Sato N et al. Frequent overexpression of epidermal growth factor receptor (EGFR) in mammary high grade ductal carcinomas with myoepithelial differentiation. J Clin Pathol, 58 (2005), 1299-1304.
  • El Guerrab A, Bamdad M, Kwiatkowski F, Bignon YJ, Penault-Llorca F, Aubel C. Anti-EGFR monoclonal antibodies and EGFR tyrosine kinase inhibitors as combination therapy for triple-negative breast cancer. Oncotarget, 7 (2016), 73618- 73637.
  • Darbeheshti F, Izadi P, Razavi ANE, Kamali F, Yekaninejad MS, Bazzaz JT. Significance of EGFR mRNA expression in luminal and triple negative breast tumors. International Journal of Cancer Management, 11 (2018), e9763.
  • Trivedi S, Srivastava RM, Concha-Benavente F, Ferrone S, Garcia-Bates TM, Li J et al. Anti-EGFR targeted monoclonal antibody isotype influences antitumor cellular immunity in head and neck cancer patients. Clin Cancer Res, 22 (2016), 5229-37.
  • Dickler MN, Cobleigh MA, Miller KD, Klein PM, Winer EP. Efficacy and safety of erlotinib in patients with locally advanced or metastatic breast cancer. Breast Cancer Res Treat, 115 (2009), 115-121.
  • Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ, Ma CX et al. TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol, 30 (2012), 2615-2623.
  • Wang F, Chen Y, Huang L, Liu T, Huang Y, Zhao J et al. Cetuximab enhanced the efficacy of chemotherapeutic agent in ABCB1/P-glycoprotein-overexpressing cancer cells. Oncotarget, 6 (2015), 40850-40865.
  • Tanei T, Choi DS, Rodriguez AA, Liang DH, Dobrolecki L, Ghosh M et al. Antitumor activity of Cetuximab in combination with Ixabepilone on triple negative breast cancer stem cells. Breast Cancer Research, 18 (2016), 6.
  • Brand TM, Iida M, EF Dunn, Luthar N, Kostopoulos KT, Corrigan KL et al. Nuclear Epidermal Growth Factor Receptor Is a Functional Molecular Target in Triple-Negative Breast Cancer. Mol Cancer Ther, 13, (2014), 1356-68.
  • Liao WS, Ho Y, Yu-Wei Lin YW, Raj EN, Liu KK, Chen C. Targeting EGFR of triple-negative breast cancer enhances the therapeutic efficacy of paclitaxel- and cetuximab-conjugated nanodiamond nanocomposite. Acta Biomaterialia, 86 (2019), 395-405.
  • Oliveras-Ferraros C, Vazquez-Martin A, López-Bonet E, Martín-Castillo B, Del Barco S, Brunet J et al. Growth and molecular interactions of the anti-EGFR antibody Cetuximab and the DNA cross-linking agent cisplatin in gefitinib-resistant MDA-MB-468 cells: New prospects in the treatment of triple-negative/basal-like breast cancer. International Journal of Oncology, 33 (2008), 1165-1176.
Year 2020, , 706 - 711, 30.09.2020
https://doi.org/10.17776/csj.751778

Abstract

Project Number

FBA-2017-24288

References

  • Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res, 13(2007), 4429-34.
  • Criscitiello C, Azim HA, Schouten PC, Linn SC, Sotiriou C. Understanding the biology of triple-negative breast cancer, Annals of Oncology, 23 (2012), vi13-vi18.
  • Buettner R, Mora LB, Jove R. Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res, 8 (2002), 945-54.
  • Hamid O. Emerging treatments in oncology: focus on tyrosine kinase (erbB) receptor inhibitors. J Am Pharm Assoc, 44 (2004), 52-8.
  • Galizia G, Lieto E, De Vita F, Orditura M, Castellano P, Troiani T et al. Cetuximab, a chimeric human mouse anti-epidermal growth factor receptor monoclonal antibody, in the treatment of human colorectal cancer. Oncogene, 26 (2007), 3654-60.
  • Martinelli E, De Palma R, Orditura M, De Vita F, Ciardiello F. Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy. Clin Exp Immunol, 158 (2009), 1-9.
  • Koukourakis MI, Tsoutsou PG, Karpouzis A, Tsiarkatsi M, Karapantzos I, Daniilidis V et al. Radiochemotherapy with cetuximab, cisplatin, and amifostine for locally advanced head and neck cancer: a feasibility study. Int J Radiat Oncol Biol Phys, 77 (2010), 9-15.
  • Muthu M, Cheriyan VT, Rishi AK. CARP-1 / CCAR1: A biphasic regulator of cancer cell growth and apoptosis. Oncotarget, 6 (2015), 6499-6510.
  • Van de Rijn M, Perou CM, Tibshirani R, Haas P, Kallioniemi O, Kononen J et al. Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol, 161 (2002), 1991-1996.
  • Shin BK, Lee Y, Lee JB, Kim HK, Lee JB, Cho SJ et al. Breast carcinomas expressing basal markers have poor clinical outcome regardless of estrogen receptor status. Oncol Rep, 19 (2008), 617-625.
  • Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA, 98 (2001), 10869-10874.
  • Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA, 100 (2003), 8418-8423.
  • Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, Jazaeri A et al. Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci USA, 100 (2003), 10393-10398.
  • Banerjee S, Reis‐Filho JS, Ashley S, Steele D, Ashworth A, Lakhani SR et al. Basal-like breast carcinomas: clinical outcome and response to chemotherapy. J Clin Pathol, 59 (2006), 729-735.
  • Lehmann BD, Pietenpol JA, Tan AR. Triple-negative breast cancer: molecular subtypes and new targets for therapy. Am Soc Clin Oncol Educ Book, 35 (2015), e31-e39.
  • Uhm JE, Park YH, Yi SY, Cho EY, Choi YL, Lee SJ et al. Treatment outcomes and clinicopathologic characteristics of triple-negative breast cancer patients who received platinum-containing chemotherapy. Int J Cancer, 124 (2009), 1457-1462.
  • Baselga J, Arteaga CL. Critical update and emerging trends in epidermal growth factor receptor targeting in cancer. J Clin Oncol, 23 (2005), 2445–59.
  • Viale G, Rotmensz N, Maisonneuve P, Bottiglieri L, Montagna E, Luini A et al. Invasive ductal carcinoma of the breast with the “triple-negative” phenotype: prognostic implications of EGFR immunoreactivity. Breast Cancer Res Treat, 116 (2009), 317-328.
  • Nielsen TO, Hsu FD, Jensen K, Cheang M, Karaca G, Hu Z et al. Immunohistochemical and clinical characterization of the basal-like subtype of invasive breast carcinoma. Clin Cancer Res, 10 (2004), 5367-5374.
  • Kim MJ, Ro JY, Ahn SH, Kim HH, Kim SB, Gong G. Clinicopathologic significance of the basal-like subtype of breast cancer: a comparison with hormone receptor and Her2/ neu-overexpressing phenotypes. Hum Pathol 37 (2006), 1217-1226.
  • Liu H, Fan Q, Zhang Z, Yu H, Meng F. Basal-HER2 phenotype shows poorer survival than basal-like phenotype in hormone receptor-negative invasive breast cancers. Hum Pathol, 39 (2008), 167-174.
  • Shien T, Tashiro T, Omatsu M, Masuda T, Furuta K, Sato N et al. Frequent overexpression of epidermal growth factor receptor (EGFR) in mammary high grade ductal carcinomas with myoepithelial differentiation. J Clin Pathol, 58 (2005), 1299-1304.
  • El Guerrab A, Bamdad M, Kwiatkowski F, Bignon YJ, Penault-Llorca F, Aubel C. Anti-EGFR monoclonal antibodies and EGFR tyrosine kinase inhibitors as combination therapy for triple-negative breast cancer. Oncotarget, 7 (2016), 73618- 73637.
  • Darbeheshti F, Izadi P, Razavi ANE, Kamali F, Yekaninejad MS, Bazzaz JT. Significance of EGFR mRNA expression in luminal and triple negative breast tumors. International Journal of Cancer Management, 11 (2018), e9763.
  • Trivedi S, Srivastava RM, Concha-Benavente F, Ferrone S, Garcia-Bates TM, Li J et al. Anti-EGFR targeted monoclonal antibody isotype influences antitumor cellular immunity in head and neck cancer patients. Clin Cancer Res, 22 (2016), 5229-37.
  • Dickler MN, Cobleigh MA, Miller KD, Klein PM, Winer EP. Efficacy and safety of erlotinib in patients with locally advanced or metastatic breast cancer. Breast Cancer Res Treat, 115 (2009), 115-121.
  • Carey LA, Rugo HS, Marcom PK, Mayer EL, Esteva FJ, Ma CX et al. TBCRC 001: randomized phase II study of cetuximab in combination with carboplatin in stage IV triple-negative breast cancer. J Clin Oncol, 30 (2012), 2615-2623.
  • Wang F, Chen Y, Huang L, Liu T, Huang Y, Zhao J et al. Cetuximab enhanced the efficacy of chemotherapeutic agent in ABCB1/P-glycoprotein-overexpressing cancer cells. Oncotarget, 6 (2015), 40850-40865.
  • Tanei T, Choi DS, Rodriguez AA, Liang DH, Dobrolecki L, Ghosh M et al. Antitumor activity of Cetuximab in combination with Ixabepilone on triple negative breast cancer stem cells. Breast Cancer Research, 18 (2016), 6.
  • Brand TM, Iida M, EF Dunn, Luthar N, Kostopoulos KT, Corrigan KL et al. Nuclear Epidermal Growth Factor Receptor Is a Functional Molecular Target in Triple-Negative Breast Cancer. Mol Cancer Ther, 13, (2014), 1356-68.
  • Liao WS, Ho Y, Yu-Wei Lin YW, Raj EN, Liu KK, Chen C. Targeting EGFR of triple-negative breast cancer enhances the therapeutic efficacy of paclitaxel- and cetuximab-conjugated nanodiamond nanocomposite. Acta Biomaterialia, 86 (2019), 395-405.
  • Oliveras-Ferraros C, Vazquez-Martin A, López-Bonet E, Martín-Castillo B, Del Barco S, Brunet J et al. Growth and molecular interactions of the anti-EGFR antibody Cetuximab and the DNA cross-linking agent cisplatin in gefitinib-resistant MDA-MB-468 cells: New prospects in the treatment of triple-negative/basal-like breast cancer. International Journal of Oncology, 33 (2008), 1165-1176.
There are 32 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section Natural Sciences
Authors

İdil Çetin 0000-0002-3961-6422

Project Number FBA-2017-24288
Publication Date September 30, 2020
Submission Date June 12, 2020
Acceptance Date September 1, 2020
Published in Issue Year 2020

Cite

APA Çetin, İ. (2020). Antiproliferative effects of cetuximab on triple negative breast cancer cell line MDA-MB-231. Cumhuriyet Science Journal, 41(3), 706-711. https://doi.org/10.17776/csj.751778