Novel Imidazo[2,1-b]oxazole Derivatives Inhibit Epithelial Cell Transformation and Triple Negative Breast Cancer Tumorigenesis

被引：5

作者：

Bhattarai, Poshan Yugal ^{[1
]}

Oh, Chang-Hyun ^{[2
]}

Kim, Garam ^{[1
]}

Kim, Min Soo ^{[1
]}

Lee, Bong Sang ^{[3
]}

Choi, Hong Seok ^{[1
]}

机构：

[1] Chosun Univ, Coll Pharm, 309 Pilmun Daero, Gwangju 501759, South Korea

[2] Korea Inst Sci & Technol, Dept Ctr Biomat, Seoul, South Korea

[3] CTCScience Inc, Hwaseong, South Korea

来源：

ANTICANCER RESEARCH | 2020年 / 40卷 / 09期

关键词：

Imidazo[2,1-b]oxazole derivatives; RAF inhibitors; TNBC; chemotherapy; TARGETED INHIBITION; SIGNALING PATHWAYS; RAF KINASES; AP-1; BRAF; ACTIVATION; EXPRESSION; PROGRESS;

D O I：

10.21873/anticanres.14511

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background/Aim: Triple negative breast cancer (TNBC) is an aggressive type of breast cancer with limited targets for chemotherapy. This study evaluated the inhibitory effects of novel imidazo[2,1-b]oxazole-based rapidly accelerated fibrosarcoma (RAF) inhibitors, KIS719215-1 and KISI19215-2, on epithelial cell transformation and TNBC tumorigenesis. Materials and Methods: Immunoblotting, BrdU incorporation assay, reporter gene assay, and soft agar assay analyses were performed. In vivo effects were studied using the BALB/c mouse xenograft model. Results: KIS719215-1 and KIS719215-2 inhibited the RAFs-MEK1/2-ERK1/2 signalling pathway induced by EGF in MDA-MB-231 cells, which inhibited c-fos transcriptional activity and activator protein-1 transactivation activity. KIST0215-1 and KIS70215-2 also prevented neoplastic transformation of .1B6 CI41 mouse epidermal cells induced by EGF and consistently suppressed the growth of tumours formed by 4TI cells in BALB/c mice. Conclusion: Inhibition of RAF kinases using KIST0215-1 and KIST0215-2 is a promising chemotherapeutic strategy to treat TNBC.

引用

页码：5081 / 5090

页数：10

共 36 条

[1] Design, synthesis, and anticancer activity of imidazo[2,1-b]oxazole-based RAF kinase inhibitors [J].

Abdel-Maksoud, Mohammed S. ;

Ammar, Usama M. ;

El-Gamal, Mohammed I. ;

El-Din, Mahmoud M. Gamal ;

Mersal, Karim I. ;

Ali, Eslam M. H. ;

Yoo, Kyung Ho ;

Lee, Kyung-Tae ;

Oh, Chang-Hyun .

BIOORGANIC CHEMISTRY, 2019, 93

[2]

[Anonymous], 2013, Hered. Genet

[3] High ERK Protein Expression Levels Correlate with Shorter Survival in Triple-Negative Breast Cancer Patients [J].

Bartholomeusz, Chandra ;

Gonzalez-Angulo, Ana M. ;

Liu, Ping ;

Hayashi, Naoki ;

Lluch, Ana ;

Ferrer-Lozano, Jaime ;

Hortobagyi, Gabriel N. .

ONCOLOGIST, 2012, 17 (06) :766-774

[4]

Baselga J, 2009, CANCER RES, V69, P45, DOI DOI 10.1158/0008-5472.SABCS-09-45

[5] RESILIENCE: Phase III Randomized, Double-Blind Trial Comparing Sorafenib With Capecitabine Versus Placebo With Capecitabine in Locally Advanced or Metastatic HER2-Negative Breast Cancer [J].

Baselga, Jose ;

Zamagni, Claudio ;

Gomez, Patricia ;

Bermejo, Begona ;

Nagai, Shigenori E. ;

Melichar, Bohuslav ;

Chan, Arlene ;

Mangel, Laszlo ;

Bergh, Jonas ;

Costa, Frederico ;

Gomez, Henry L. ;

Gradishar, William J. ;

Hudis, Clifford A. ;

Rapoport, Bernardo L. ;

Roche, Henri ;

Maeda, Patricia ;

Huang, Liping ;

Meinhardt, Gerold ;

Zhang, Joshua ;

Schwartzberg, Lee S. .

CLINICAL BREAST CANCER, 2017, 17 (08) :585-+

[6] A phase 3 tRial comparing capecitabinE in combination with SorafenIb or pLacebo for treatment of locally advanced or metastatIc HER2-Negative breast CancEr (the RESILIENCE study): study protocol for a randomized controlled trial [J].

Baselga, Jose ;

Costa, Frederico ;

Gomez, Henry ;

Hudis, Clifford A. ;

Rapoport, Bernardo ;

Roche, Henri ;

Schwartzberg, Lee S. ;

Petrenciuc, Oana ;

Shan, Minghua ;

Gradishar, William J. .

TRIALS, 2013, 14

[7]

Beniey Michele, 2019, Oncoscience, V6, P287, DOI 10.18632/oncoscience.474

[8] Function and regulation in MAPK signaling pathways:: Lessons learned from the yeast Saccharomyces cerevisiae [J].

Chen, Raymond E. ;

Thorner, Jeremy .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2007, 1773 (08) :1311-1340

[9] Triple-Negative Breast Cancer: The Progress of Targeted Therapies and Future Tendencies [J].

Damaskos, Christos ;

Garmpi, Anna ;

Nikolettos, Konstantinos ;

Vavourakis, Michail ;

Diamantis, Evangelos ;

Patsouras, Alexandros ;

Farmaki, Paraskevi ;

Nonni, Afroditi ;

Dimitroulis, Dimitrios ;

Mantas, Dimitrios ;

Antoniou, Efstathios A. ;

Nikolettos, Nikos ;

Kontzoglou, Konstantinos ;

Garmpis, Nikolaos .

ANTICANCER RESEARCH, 2019, 39 (10) :5285-5296

[10] The RAS/RAF/MEK/ERK and the PI3K/AKT signalling pathways: role in cancer pathogenesis and implications for therapeutic approaches [J].

De Luca, Antonella ;

Maiello, Monica R. ;

D'Alessio, Amelia ;

Pergameno, Maria ;

Normanno, Nicola .

EXPERT OPINION ON THERAPEUTIC TARGETS, 2012, 16 :S17-S27

← 1 2 3 4 →