Browse > Article
http://dx.doi.org/10.4174/astr.2018.95.5.240

ABT-737 ameliorates docetaxel resistance in triple negative breast cancer cell line  

Hwang, Eunjoo (Department of Surgery, Seoul Metropolitan Government - Seoul National University Boramae Medical Center)
Hwang, Seong-Hye (Department of Surgery, Seoul Metropolitan Government - Seoul National University Boramae Medical Center)
Kim, Jongjin (Department of Surgery, Seoul Metropolitan Government - Seoul National University Boramae Medical Center)
Park, Jin Hyun (Department of Internal Medicine, Seoul Metropolitan Government - Seoul National University Boramae Medical Center)
Oh, Sohee (Department of Biostatistics, Seoul Metropolitan Government - Seoul National University Boramae Medical Center)
Kim, Young A (Department of Pathology, Seoul Metropolitan Government - Seoul National University Boramae Medical Center)
Hwang, Ki-Tae (Department of Surgery, Seoul Metropolitan Government - Seoul National University Boramae Medical Center)
Publication Information
Annals of Surgical Treatment and Research / v.95, no.5, 2018 , pp. 240-248 More about this Journal
Abstract
Purpose: This study aimed to validate the synergistic effect of ABT-737 on docetaxel using MDA-MB-231, a triple negative breast cancer (TNBC) cell line overexpressing B-cell lymphoma-2 (Bcl-2). Methods: Western blot analysis was performed to assess expression levels of Bcl-2 family proteins and caspase-related molecules. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell cycle distribution was determined by flow cytometry analysis. Benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (z-VAD-fmk) was used for pretreatment to assess the role of caspases. Results: Cell viability of MDA-MB-231 after combination treatment with ABT-737 and docetaxel was significantly lower than that after docetaxel or ABT-737 monotherapy based on MTT assay (both P < 0.001), with a combination index of 0.41. The proportion of sub-G1 population after combination treatment was significantly higher than that after docetaxel or ABT-737 monotherapy (P = 0.001, P = 0.003, respectively). Pretreatment with z-VAD-fmk completely restored cell viability of MDA-MB-231 from apoptotic cell death induced by combination therapy (P = 0.001). Although pro-caspase-8 or Bid did not show significant change in expression level, pro-casepase-9 showed significantly decreased expression after combination treatment. Cleaved caspase-3 showed increased expression while poly (ADP-ribose) polymerase cleavage was induced after combination treatment. However, hypoxia-inducible factor 1-alpha and aldehyde dehydrogenase 1 totally lost their expression after combination treatment. Conclusion: Combination of ABT-737 with docetaxel elicits synergistic therapeutic effect on MDA-MB-231, a TNBC cell line overexpressing Bcl-2, mainly by activating the intrinsic pathway of apoptosis. Therefore, adjunct of ABT-737 to docetaxel might be a new therapeutic option to overcome docetaxel resistance of TNBCs overexpressing Bcl-2.
Keywords
ABT-737; Bcl-2; Docetaxel; Drug resistance; Triple negative breast neoplasms;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Foulkes WD, Smith IE, Reis-Filho JS. Triple-negative breast cancer. N Engl J Med 2010;363:1938-48.   DOI
2 Carey L, Winer E, Viale G, Cameron D, Gianni L. Triple-negative breast cancer: disease entity or title of convenience? Nat Rev Clin Oncol 2010;7:683-92.   DOI
3 Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK, Sawka CA, et al. Triplenegative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007;13(15 Pt 1):4429-34.   DOI
4 Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol 2014;15:49-63.   DOI
5 Tsujimoto Y, Finger LR, Yunis J, Nowell PC, Croce CM. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation. Science 1984;226:1097-9.   DOI
6 Hwang KT, Woo JW, Shin HC, Kim HS, Ahn SK, Moon HG, et al. Prognostic influence of BCL2 expression in breast cancer. Int J Cancer 2012;131:E1109-19.   DOI
7 Hwang KT, Han W, Kim J, Moon HG, Oh S, Song YS, et al. Prognostic influence of Bcl2 on molecular subtypes of breast cancer. J Breast Cancer 2017;20:54-64.   DOI
8 Dawson SJ, Makretsov N, Blows FM, Driver KE, Provenzano E, Le Quesne J, et al. BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received. Br J Cancer 2010;103:668-75.   DOI
9 Callagy GM, Webber MJ, Pharoah PD, Caldas C. Meta-analysis confirms BCL2 is an independent prognostic marker in breast cancer. BMC Cancer 2008;8:153.   DOI
10 Liedtke C, Mazouni C, Hess KR, Andre F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol 2008;26:1275-81.   DOI
11 Cragg MS, Harris C, Strasser A, Scott CL. Unleashing the power of inhibitors of oncogenic kinases through BH3 mimetics. Nat Rev Cancer 2009;9:321-6.   DOI
12 Oakes SR, Vaillant F, Lim E, Lee L, Breslin K, Feleppa F, et al. Sensitization of BCL-2-expressing breast tumors to chemotherapy by the BH3 mimetic ABT-737. Proc Natl Acad Sci U S A 2012;109:2766-71.   DOI
13 Panayotopoulou EG, Muller AK, Borries M, Busch H, Hu G, Lev S. Targeting of apoptotic pathways by SMAC or BH3 mimetics distinctly sensitizes paclitaxelresistant triple negative breast cancer cells. Oncotarget 2017;8:45088-104.
14 Kutuk O, Letai A. Alteration of the mitochondrial apoptotic pathway is key to acquired paclitaxel resistance and can be reversed by ABT-737. Cancer Res 2008;68:7985-94.   DOI
15 Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-54.   DOI
16 Mayer IA, Abramson VG, Lehmann BD, Pietenpol JA. New strategies for triplenegative breast cancer--deciphering the heterogeneity. Clin Cancer Res 2014;20:782-90.   DOI
17 Witham J, Valenti MR, De-Haven-Brandon AK, Vidot S, Eccles SA, Kaye SB, et al. The Bcl-2/Bcl-XL family inhibitor ABT-737 sensitizes ovarian cancer cells to carboplatin. Clin Cancer Res 2007;13:7191-8.   DOI
18 Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22:27-55.   DOI
19 Abramson VG, Lehmann BD, Ballinger TJ, Pietenpol JA. Subtyping of triple-negative breast cancer: implications for therapy. Cancer 2015;121:8-16.   DOI
20 Rooswinkel RW, van de Kooij B, Verheij M, Borst J. Bcl-2 is a better ABT-737 target than Bcl-xL or Bcl-w and only Noxa overcomes resistance mediated by Mcl-1, Bfl-1, or Bcl-B. Cell Death Dis 2012;3:e366.   DOI
21 Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death. N Engl J Med 2009;361:1570-83.   DOI
22 Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell 2004;116:205-19.   DOI
23 Ajabnoor GM, Crook T, Coley HM. Paclitaxel resistance is associated with switch from apoptotic to autophagic cell death in MCF-7 breast cancer cells. Cell Death Dis 2012;3:e260.   DOI
24 Kepp O, Galluzzi L, Lipinski M, Yuan J, Kroemer G. Cell death assays for drug discovery. Nat Rev Drug Discov 2011;10:221-37.   DOI
25 Ichim G, Tait SW. A fate worse than death: apoptosis as an oncogenic process. Nat Rev Cancer 2016;16:539-48.   DOI
26 Ginestier C, Hur MH, Charafe-Jauffret E, Monville F, Dutcher J, Brown M, et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 2007;1:555-67.   DOI
27 Herceg Z, Wang ZQ. Functions of poly (ADP-ribose) polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat Res 2001;477:97-110.   DOI
28 Samanta D, Gilkes DM, Chaturvedi P, Xiang L, Semenza GL. Hypoxia-inducible factors are required for chemotherapy resistance of breast cancer stem cells. Proc Natl Acad Sci U S A 2014;111:E5429-38.   DOI
29 Chen CH, Ferreira JC, Gross ER, Mochly-Rosen D. Targeting aldehyde dehydrogenase 2: new therapeutic opportunities. Physiol Rev 2014;94:1-34.   DOI
30 Kida K, Ishikawa T, Yamada A, Shimada K, Narui K, Sugae S, et al. Effect of ALDH1 on prognosis and chemoresistance by breast cancer subtype. Breast Cancer Res Treat 2016;156:261-9.   DOI