Anti-cancer effects of the combined treatment of trastuzumab and decoy oligodeoxynucleotides to target STAT3 transcription factor on SK-BR-3 breast cancer cell line

Behrooz Johari; Roghayeh Ghorbani; Sara Heidari; Somayyeh Rashidi; Hamid Madanchi

Anti-cancer effects of the combined treatment of trastuzumab and decoy oligodeoxynucleotides to target STAT3 transcription factor on SK-BR-3 breast cancer cell line

authors:

Behrooz Johari , Roghayeh Ghorbani ^{, *} , Sara Heidari , Somayyeh Rashidi , Hamid Madanchi

Koomesh: Vol.25, issue 1; 71-82

article type: issue_documents_importer

received: June 01, 2022

accepted: November 03, 2022

how to cite: Johari B, Ghorbani R, Heidari S, Rashidi S, Madanchi H. Anti-cancer effects of the combined treatment of trastuzumab and decoy oligodeoxynucleotides to target STAT3 transcription factor on SK-BR-3 breast cancer cell line. koomesh. 2023;25(1):e152804.

Abstract

Introduction: Breast cancer is the most common malignancy in the female population and is the leading cause of death. Surgery, chemotherapy, radiotherapy, and monoclonal antibody (trastuzumab) therapy are common and standard treatments for this cancer. However, there are significant limitations in the treatment of this disease by using regular methods. Given the role of transcription factors (TFs) in gene expression, differentiation therapy, and many cancer signaling pathways, in the present study, the effect of combined treatment of trastuzumab (Herceptin) and decoy oligodeoxynucleotides to target the STAT3 transcription factor on inhibition of HER2 positive SK-BR-3 cell line growth was investigated. Materials and Methods: At first, different concentrations of Trastuzumab were prepared from 0.1 to 100 μg/mL. In this way, the decoy and scramble oligodeoxynucleotides were designed and synthesized to target the STAT3 transcription factor. The transfection efficiency and combined effects of trastuzumab with decoy oligos on cell viability, apoptosis, and cell migration inhibition were evaluated. Results: The results showed that oligodeoxynucleotides labeled with Cy3 fluorophore (300 nM) enter the cells with high efficiency (81.7±6.9%). Combined treatment of cells by trastuzumab (10 μg/mL) along with decoy oligodeoxynucleotides (100 nM) led to a decrease in cell viability (58.86±2.71%), increased apoptosis (24.54±4.83%) and inhibited cell migration (45.95±4.21%). Conclusion: The results from this study showed the anticancer effects of combination therapy using trastuzumab with decoy oligodeoxynucleotides to target the STAT3 transcription factor in SK-BR-3 cells. Therefore, it seems that this strategy can be used as an adjunct to common treatments for breast cancer.

Keywords

Breast cancer HER2 receptor Oligodeoxynucleotide decoy STAT3 transcription factor Apoptosis Cell migration سرطان پستان گیرنده HER2 الیگودئوکسی نوکلئوتید تله فاکتور رونویسی STAT3 آپوپتوز مهاجرت سلولی

References

1.
Xia C, Dong X, Li H, Cao M, Sun D, He S, et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants. Chin Med J 2022; 135: 584-590. [PubMed ID: 35143424 PMCid:PMC8920425]. https://doi.org/https://doi.org/10.1097/CM9.0000000000002108.
2.
Dhankhar R, Vyas SP, Jain AK, Arora S, Rath G, Goyal AK. Advances in novel drug delivery strategies for breast cancer therapy. Artificial cells, blood substitutes, and immobilization biotechnology. 2010; 38: 230-249. [PubMed ID: 20677900]. https://doi.org/https://doi.org/10.3109/10731199.2010.494578.
3.
Wu Q, Yang Z, Nie Y, Shi Y, Fan D. Multi-drug resistance in cancer chemotherapeutics: mechanisms and lab approaches. Cancer Lett 2014; 347: 159-166. [PubMed ID: https://doi.org/10.1016/j.canlet.2014.03.013##24657660]. https://doi.org/https://doi.org/10.1016/j.canlet.2014.08.044.
4.
Prez-Herrero E, Fernndez-Medarde A. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. Eur J Pharm Biopharm 2015; 93: 52-79. [PubMed ID: 25813885]. https://doi.org/https://doi.org/10.1016/j.ejpb.2015.03.018.
5.
Mi Y, Shao Z, Vang J, Kaidar-Person O, Wang AZ. Application of nanotechnology to cancer radiotherapy. Cancer Nanotechnol 2016; 7: 1-16. [PubMed ID: 28066513 PMCid:PMC5167776]. https://doi.org/https://doi.org/10.1186/s12645-016-0024-7.
6.
Borrebaeck CA, Carlsson R. Human therapeutic antibodies. Curr Opin Pharmacol 2001; 1: 404-408. [PubMed ID: 11710740]. https://doi.org/https://doi.org/10.1016/S1471-4892(01)00070-4.
7.
Hansel TT, Kropshofer H, Singer T, Mitchell JA, George AJ. The safety and side effects of monoclonal antibodies. Nat Rev Drug Discov 2010; 9: 325-338. [PubMed ID: 20305665]. https://doi.org/https://doi.org/10.1038/nrd3003.
8.
Sell S. Stem cell origin of cancer and differentiation therapy. Crit Rev Oncol Hematol 2004; 51: 1-28. [PubMed ID: 15207251]. https://doi.org/https://doi.org/10.1016/j.critrevonc.2004.04.007.
9.
Hecker M, Wagner AH. Transcription factor decoy technology: A therapeutic update. Biochem Pharmacol 2017; 144: 29-34. [PubMed ID: 28642036]. https://doi.org/https://doi.org/10.1016/j.bcp.2017.06.122.
10.
Huynh J, Chand A, Gough D, Ernst M. Therapeutically exploiting STAT3 activity in cancer-using tissue repair as a road map. Nat Rev Cancer 2019; 19: 82-96. [PubMed ID: 30578415]. https://doi.org/https://doi.org/10.1038/s41568-018-0090-8.
11.
Ma JH, Qin L, Li X. Role of STAT3 signaling pathway in breast cancer. Cell Commun Signal 2020; 18: 1-13. [PubMed ID: 32111215 PMCid:PMC7048131]. https://doi.org/https://doi.org/10.1186/s12964-020-0527-z.
12.
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-674. [PubMed ID: 21376230]. https://doi.org/https://doi.org/10.1016/j.cell.2011.02.013.
13.
Mitsuyama K, Matsumoto S, Masuda J, Yamasaki H, Kuwaki K, Takedatsu H, et al. Therapeutic strategies for targeting the IL-6/STAT3 cytokine signaling pathway in inflammatory bowel disease. Anticancer Res 2007; 27: 3749-3756.
14.
Lo HW, Hsu SC, Ali-Seyed M, Gunduz M, Xia W, Wei Y, et al. Nuclear interaction of EGFR and STAT3 in the activation of the iNOS/NO pathway. Cancer Cell 2005; 7: 575-589. [PubMed ID: 15950906]. https://doi.org/https://doi.org/10.1016/j.ccr.2005.05.007.
15.
Ahmed S, Sami A, Xiang J. HER2-directed therapy: current treatment options for HER2-positive breast cancer. Breast Cancer 2015; 22: 101-116. [PubMed ID: 25634227]. https://doi.org/https://doi.org/10.1007/s12282-015-0587-x.
16.
Wang T, Xu Y, Sheng S, Yuan H, Ouyang T, Li J, et al. HER2 somatic mutations are associated with poor survival in HER2-negative breast cancers. Cancer Sci 2017; 108: 671-677. [PubMed ID: 28164408 PMCid:PMC5406600]. https://doi.org/https://doi.org/10.1111/cas.13182.
17.
Connell CM, Doherty GJ. Activating HER2 mutations as emerging targets in multiple solid cancers. ESMO Open 2017; 2: e000279. [PubMed ID: 29209536 PMCid:PMC5708307]. https://doi.org/https://doi.org/10.1136/esmoopen-2017-000279.
18.
Li R, Chibbar R, Xiang J. Novel EXO-T vaccine using polyclonal CD4(+) T cells armed with HER2-specific exosomes for HER2-positive breast cancer. Onco Targets Ther 2018; 11: 7089-7093. [PubMed ID: 30410365 PMCid:PMC6200095]. https://doi.org/https://doi.org/10.2147/OTT.S184898.
19.
Torti SV, Torti FM. Cellular iron metabolism in prognosis and therapy of breast cancer. Crit Rev Oncog 2013; 18: 435-448. [PubMed ID: 23879588 PMCid:PMC3736347]. https://doi.org/https://doi.org/10.1615/CritRevOncog.2013007784.
20.
Crawford A, Nahta R. Targeting Bcl-2 in herceptin-resistant breast cancer cell lines. Curr Pharmacogenomics Person Med 2011; 9: 184-190. [PubMed ID: 22162984 PMCid:PMC3233239]. https://doi.org/https://doi.org/10.2174/187569211796957584.
21.
Cui H, Cheng Y, Piao SZ, Xu YJ, Sun HH, Cui X, et al. Correlation between HER-2/neu(erbB-2) expression level and therapeutic effect of combination treatment with HERCEPTIN and chemotherapeutic agents in gastric cancer cell lines. Cancer Cell Int 2014; 14: 10. [PubMed ID: 24472145 PMCid:PMC3915235]. https://doi.org/https://doi.org/10.1186/1475-2867-14-10.
22.
Adams GP, Weiner LM. Monoclonal antibody therapy of cancer. Nat Biotechnol 2005; 23: 1147-1157. [PubMed ID: 16151408]. https://doi.org/https://doi.org/10.1038/nbt1137.
23.
Hajighasemlou S, Alebouyeh M, Rastegar H, Manzari MT, Mirmoghtadaei M, Moayedi B, et al. Preparation of immunotoxin herceptin-botulinum and killing effects on two breast cancer cell lines. Asian Pac J Cancer Prev 2015; 16: 5977-5981. [PubMed ID: 26320483]. https://doi.org/https://doi.org/10.7314/APJCP.2015.16.14.5977.
24.
Wang N, Wei L, Huang Y, Wu Y, Su M, Pang X, et al. miR520c blocks EMT progression of human breast cancer cells by repressing STAT3. Oncol Rep 2017; 37: 1537-1544. [PubMed ID: 28112380]. https://doi.org/https://doi.org/10.3892/or.2017.5393.
25.
Bielinska A, Shivdasani RA, Zhang LQ, Nabel GJ. Regulation of gene expression with double-stranded phosphorothioate oligonucleotides. Science 1990; 250: 997-1000. [PubMed ID: 2237444]. https://doi.org/https://doi.org/10.1126/science.2237444.
26.
Morishita R, Sugimoto T, Aoki M, Kida I, Tomita N, Moriguchi A, et al. In vivo transfection of cis element "decoy" against nuclear factor- B binding site prevents myocardial infarction. Nat Med 1997; 3: 894. [PubMed ID: 9256281]. https://doi.org/https://doi.org/10.1038/nm0897-894.
27.
Mann MJ, Dzau VJ. Therapeutic applications of transcription factor decoy oligonucleotides. J Clin Invest 2000; 106: 1071-1075. [PubMed ID: 11067859 PMCid:PMC301425]. https://doi.org/https://doi.org/10.1172/JCI11459.
28.
Johari B, Ebrahimi-Rad M, Maghsood F, Lotfinia M, Saltanatpouri Z, Teimoori-Toolabi L, et al. Myc decoy oligodeoxynucleotide inhibits growth and modulates differentiation of mouse embryonic stem cells as a model of cancer stem cells. Anticancer Agents Med Chem 2017; 17: 1786-1795. [PubMed ID: 28403778]. https://doi.org/https://doi.org/10.2174/1871521409666170412142507.
29.
Johari B, Zargan J. Simultaneous targeted inhibition of Sox2-Oct4 transcription factors using decoy oligodeoxynucleotides to repress stemness properties in mouse embryonic stem cells. Cell Biol Int 2017; 41: 1335-1344. [PubMed ID: 28833847]. https://doi.org/https://doi.org/10.1002/cbin.10847.
30.
Rahmati M, Johari B, Kadivar M, Rismani E, Mortazavi Y. Suppressing the metastatic properties of the breast cancer cells using STAT3 decoy oligodeoxynucleotides: a promising approach for eradication of cancer cells by differentiation therapy. J Cell Physiol 2020; 235: 5429-5444. [PubMed ID: 31912904]. https://doi.org/https://doi.org/10.1002/jcp.29431.
31.
Gharbavi M, Johari B, Rismani E, Mousazadeh N, Taromchi AH, Sharafi A. NANOG decoy oligodeoxynucleotide-encapsulated niosomes nanocarriers: a promising approach to suppress the metastatic properties of U87 human glioblastoma multiforme cells. ACS Chem Neurosci 2020; 11: 4499-4515. [PubMed ID: 33283497]. https://doi.org/https://doi.org/10.1021/acschemneuro.0c00699.
32.
Sen M, Thomas SM, Kim S, Yeh JI, Ferris RL, Johnson JT, et al. First-in-human trial of a STAT3 decoy oligonucleotide in head and neck tumors: implications for cancer therapy. Cancer Discov 2012; 2: 694-705. [PubMed ID: 22719020 PMCid:PMC3668699]. https://doi.org/https://doi.org/10.1158/2159-8290.CD-12-0191.
33.
Tripathi SK, Chen Z, Larjo A, Kanduri K, Nousiainen K, ijo T, et al. Genome-wide analysis of STAT3-mediated transcription during early human Th17 cell differentiation. Cell Rep 2017; 19: 1888-1901. [PubMed ID: 28564606]. https://doi.org/https://doi.org/10.1016/j.celrep.2017.05.013.
34.
Bigdelou Z, Mortazavi Y, Saltanatpour Z, Asadi Z, Kadivar M, Johari B. Role of Oct4-Sox2 complex decoy oligodeoxynucleotides strategy on reverse epithelial to mesenchymal transition (EMT) induction in HT29-ShE encompassing enriched cancer stem-like cells. Mol Biol Rep 2020; 47: 1859-1869. [PubMed ID: 32016633]. https://doi.org/https://doi.org/10.1007/s11033-020-05280-2.
35.
Asadi Z, Fathi M, Rismani E, Bigdelou Z, Johari B. Application of decoy oligodeoxynucleotides strategy for inhibition of cell growth and reduction of metastatic properties in nonresistant and erlotinibresistant SW480 cell line. Cell Biol Int 2021; 45: 1001-1014. [PubMed ID: 33377576]. https://doi.org/https://doi.org/10.1002/cbin.11543.
36.
Johari B, Rahmati M, Nasehi L, Mortazavi Y, Faghfoori MH, Rezaeejam H. Evaluation of STAT3 decoy oligodeoxynucleotides' synergistic effects on radiation and/or chemotherapy in metastatic breast cancer cell line. Cell Biol Int 2020; 44: 2499-2511. [PubMed ID: 32841450]. https://doi.org/https://doi.org/10.1002/cbin.11456.
37.
Woosley AN, Dalton AC, Hussey GS, Howley BV, Mohanty BK, Grelet S, et al. TGF promotes breast cancer stem cell self-renewal through an ILEI/LIFR signaling axis. Oncogene 2019; 38: 3794-37811. [PubMed ID: 30692635 PMCid:PMC6525020]. https://doi.org/https://doi.org/10.1038/s41388-019-0703-z.
38.
Lambert SA, Jolma A, Campitelli LF, Das PK, Yin Y, Albu M, et al. The human transcription factors. Cell 2018; 172: 650-665. [PubMed ID: 29425488]. https://doi.org/https://doi.org/10.1016/j.cell.2018.01.029.
39.
Furtek SL, Backos DS, Matheson CJ, Reigan P. Strategies and approaches of targeting STAT3 for cancer treatment. ACS Chem Biol 2016; 11: 308-318. [PubMed ID: 26730496]. https://doi.org/https://doi.org/10.1021/acschembio.5b00945.
40.
Mitchell TJ, John S. Signal transducer and activator of transcription (STAT) signalling and Tcell lymphomas. Immunology 2005; 114: 301-312. [PubMed ID: 15720432 PMCid:PMC1782085]. https://doi.org/https://doi.org/10.1111/j.1365-2567.2005.02091.x.
41.
Senft C, Priester M, Polacin M, Schrder K, Seifert V, Kgel D, et al. Inhibition of the JAK-2/STAT3 signaling pathway impedes the migratory and invasive potential of human glioblastoma cells. J Neuro Oncol 2011; 101: 393-403. [PubMed ID: 20589525]. https://doi.org/https://doi.org/10.1007/s11060-010-0273-y.
42.
Kortylewski M, Kujawski M, Wang T, Wei S, Zhang S, Pilon-Thomas S, et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat Med 2005; 11: 1314. [PubMed ID: 16288283]. https://doi.org/https://doi.org/10.1038/nm1325.
43.
Furqan M, Akinleye A, Mukhi N, Mittal V, Chen Y, Liu D. STAT inhibitors for cancer therapy. J Hematol Oncol 2013; 6: 90. [PubMed ID: 24308725 PMCid:PMC4029528]. https://doi.org/https://doi.org/10.1186/1756-8722-6-90.
44.
Yu H, Jove R. The STATs of cancer-new molecular targets come of age. Nat Rev Cancer 2004; 4: 97. [PubMed ID: 14964307]. https://doi.org/https://doi.org/10.1038/nrc1275.
45.
Ogura M, Uchida T, Terui Y, Hayakawa F, Kobayashi Y, Taniwaki M, et al. Phase I study of OPB51602, an oral inhibitor of signal transducer and activator of transcription 3, in patients with relapsed/refractory hematological malignancies. Cancer Sci 2015; 106: 896-901. [PubMed ID: 25912076 PMCid:PMC4520642]. https://doi.org/https://doi.org/10.1111/cas.12683.
46.
Oh DY, Lee SH, Han SW, Kim MJ, Kim TM, Kim TY, et al. Phase I study of OPB-31121, an oral STAT3 inhibitor, in patients with advanced solid tumors. Cancer Res Treat 2015; 47: 607. [PubMed ID: 25715763 PMCid:PMC4614199]. https://doi.org/https://doi.org/10.4143/crt.2014.249.
47.
Rad SM, Langroudi L, Kouhkan F, Yazdani L, Koupaee AN, Asgharpour S, et al. Transcription factor decoy: a pre-transcriptional approach for gene downregulation purpose in cancer. Tumor Biol 2015; 36: 4871-4881. [PubMed ID: 25835969]. https://doi.org/https://doi.org/10.1007/s13277-015-3344-z.
48.
Mann MJ. Transcription factor decoys: a new model for disease intervention. Ann N Y Acad Sci 2005; 1058: 128-139. [PubMed ID: 16394132]. https://doi.org/https://doi.org/10.1196/annals.1359.021.
49.
Horton J. Trastuzumab use in breast cancer: clinical issues. Cancer Control 2002; 9: 499-507. [PubMed ID: 12514568]. https://doi.org/https://doi.org/10.1177/107327480200900607.
50.
Rad SM, Bamdad T, Sadeghizadeh M, Arefian E, Lotfinia M, Ghanipour M. Transcription factor decoy against stem cells master regulators, Nanog and Oct-4: a possible approach for differentiation therapy. Tumor Biol 2015; 36: 2621-2629. [PubMed ID: 25464862]. https://doi.org/https://doi.org/10.1007/s13277-014-2884-y.
51.
Merlin JL, Barberi-Heyob M, Bachmann N. In vitro comparative evaluation of trastuzumab (Herceptin) combined with paclitaxel (Taxol) or docetaxel (Taxotere) in HER2-expressing human breast cancer cell lines. Ann Oncol 2002; 13: 1743-1748. [PubMed ID: 12419746]. https://doi.org/https://doi.org/10.1093/annonc/mdf263.
52.
Park S, Nedrow JR, Josefsson A, Sgouros G. Human HER2 overexpressing mouse breast cancer cell lines derived from MMTV. f. HuHER2 mice: characterization and use in a model of metastatic breast cancer. Oncotarget 2017; 8: 68071. [PubMed ID: 28978097 PMCid:PMC5620237]. https://doi.org/https://doi.org/10.18632/oncotarget.19174.
53.
Wei D, Zhang G, Zhu Z, Zheng Y, Yan F, Pan C, et al. Nobiletin inhibits cell viability via the SRC. AKT/STAT3/YY1AP1 pathway in human renal carcinoma cells. Front Pharmacol 2019. [PubMed ID: 31354472 PMCid:PMC6635658]. https://doi.org/https://doi.org/10.3389/fphar.2019.00690.
54.
Ramirez de Arellano A, Lopez-Pulido EI, Martinez-Neri PA, Estrada Chavez C, Gonzalez Lucano R, Fafutis-Morris M, et al. STAT3 activation is required for the antiapoptotic effects of prolactin in cervical cancer cells. Cancer Cell Int 2015; 15: 83. [PubMed ID: 26346346 PMCid:PMC4559880]. https://doi.org/https://doi.org/10.1186/s12935-015-0234-9.
55.
Cittelly DM, Das PM, Salvo VA, Fonseca JP, Burow ME, Jones FE. Oncogenic HER216 suppresses miR-15a/16 and deregulates BCL-2 to promote endocrine resistance of breast tumors. Carcinogenesis 2010; 31: 2049-2057. [PubMed ID: 20876285 PMCid:PMC2994280]. https://doi.org/https://doi.org/10.1093/carcin/bgq192.
56.
Chakrabarty A, Bhola NE, Sutton C, Ghosh R, Kuba MG, Dave B, et al. Trastuzumab-resistant cells rely on a HER2-PI3K-FoxO-Survivin axis and are sensitive to PI3K inhibitorsPI3K inhibition sensitizes trastuzumab-resistant cells. Cancer Res 2013; 73: 1190-1200. [PubMed ID: 23204226 PMCid:PMC3563941]. https://doi.org/https://doi.org/10.1158/0008-5472.CAN-12-2440.
57.
Real PJ, Benito A, Cuevas J, Berciano MT, de Juan A, Coffer P, et al. Blockade of epidermal growth factor receptors chemosensitizes breast cancer cells through up-regulation of Bnip3L. Cancer Res 2005; 65: 8151-8157. [PubMed ID: 16166289]. https://doi.org/https://doi.org/10.1158/0008-5472.CAN-05-1134.
58.
Oliveras-Ferraros C, Vazquez-Martin A, Cuf S, Torres-Garcia VZ, Sauri-Nadal T, Del Barco S, et al. Inhibitor of Apoptosis (IAP) survivin is indispensable for survival of HER2 gene-amplified breast cancer cells with primary resistance to HER1/2-targeted therapies. Biochem Biophys Res Commun 2011; 407: 412-419. [PubMed ID: 21402055]. https://doi.org/https://doi.org/10.1016/j.bbrc.2011.03.039.
59.
Seoane S, Montero JC, Ocaa A, Pandiella A. Effect of multikinase inhibitors on caspase-independent cell death and DNA damage in HER2-overexpressing breast cancer cells. J Nat Cancer Instit 2010; 102: 1432-1446. [PubMed ID: 20811002##]. https://doi.org/https://doi.org/10.1093/jnci/djq315.
60.
Wang J, Guo XJ, Ding YM, Jiang JX. miR-1181 inhibits invasion and proliferation via STAT3 in pancreatic cancer. World J Gastroenterol 2017; 23: 1594-1601. [PubMed ID: 28321160 PMCid:PMC5340811##]. https://doi.org/https://doi.org/10.3748/wjg.v23.i9.1594.
61.
Kulesza DW, Ramji K, Maleszewska M, Mieczkowski J, Dabrowski M, Chouaib S, et al. Search for novel STAT3-dependent genes reveals SERPINA3 as a new STAT3 target that regulates invasion of human melanoma cells. Lab Invest 2019. [PubMed ID: 31278347]. https://doi.org/https://doi.org/10.1038/s41374-019-0288-8.
62.
Franco-Cea A, Ellis SJ, Fairchild MJ, Yuan L, Cheung TYS, Tanentzapf G. Distinct developmental roles for direct and indirect talin-mediated linkage to actin. Dev Biol 2010; 345: 64-77. [PubMed ID: 20599891]. https://doi.org/https://doi.org/10.1016/j.ydbio.2010.06.027.
63.
Moser M, Legate KR, Zent R, Fssler R. The tail of integrins, talin, and kindlins. Science 2009; 324: 895-899. [PubMed ID: 19443776]. https://doi.org/https://doi.org/10.1126/science.1163865.
64.
Levy DE, Lee CK. What does Stat3 do? J Clin Invest 2002; 109: 1143-1148. [PubMed ID: 11994402 PMCid:PMC150972]. https://doi.org/https://doi.org/10.1172/JCI0215650.

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Anti-cancer effects of the combined treatment of trastuzumab and decoy oligodeoxynucleotides to target STAT3 transcription factor on SK-BR-3 breast cancer cell line

Abstract

Keywords

References

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