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Research ArticleExperimental Studies

Nebivolol Sensitizes BT-474 Breast Cancer Cells to FGFR Inhibitors

YU JIN KIM, SE-KYEONG JANG, GYEONGMI KIM, SUNG-EUN HONG, CHAN SUB PARK, MIN-KI SEONG, HYUN-AH KIM, KWANG SEOK KIM, CHUN-HO KIM, KI SOO PARK, JUNGIL HONG, HYEON-OK JIN and IN-CHUL PARK
Anticancer Research May 2023, 43 (5) 1973-1980; DOI: https://doi.org/10.21873/anticanres.16357
YU JIN KIM
1Division of Fusion Radiology Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea;
2Department of Biological Engineering, Konkuk University, Seoul, Republic of Korea;
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SE-KYEONG JANG
1Division of Fusion Radiology Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea;
3Department of Food and Microbial Technology, Seoul Women’s University, Seoul, Republic of Korea;
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GYEONGMI KIM
1Division of Fusion Radiology Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea;
4Department of Cosmetics Engineering, Konkuk University, Seoul, Republic of Korea;
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SUNG-EUN HONG
5KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea;
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CHAN SUB PARK
6Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea;
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MIN-KI SEONG
6Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea;
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HYUN-AH KIM
6Department of Surgery, Korea Cancer Center Hospital, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea;
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KWANG SEOK KIM
1Division of Fusion Radiology Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea;
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CHUN-HO KIM
7Laboratory of Tissue Engineering, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea
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KI SOO PARK
2Department of Biological Engineering, Konkuk University, Seoul, Republic of Korea;
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JUNGIL HONG
3Department of Food and Microbial Technology, Seoul Women’s University, Seoul, Republic of Korea;
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HYEON-OK JIN
5KIRAMS Radiation Biobank, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea;
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IN-CHUL PARK
1Division of Fusion Radiology Research, Korea Institute of Radiological & Medical Sciences, Seoul, Republic of Korea;
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  • For correspondence: parkic@kirams.re.kr
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Abstract

Background/Aim: The fibroblast growth factor receptor (FGFR) signaling pathway is abnormally activated in human cancers, including breast cancer. Therefore, targeting the FGFR signaling pathway is a potent strategy to treat breast cancer. The purpose of this study was to find drugs that could increase sensitivity to FGFR inhibitor effects in BT-474 breast cancer cells, and to investigate the combined effects and underlying mechanisms of these combinations for BT-474 breast cancer cell survival. Materials and Methods: Cell viability was measured by MTT assay. Protein expression was determined by western blot analysis. mRNA expression was detected by Real-time PCR. Drug synergy effect was determined by isobologram analysis. Results: Nebivolol, a third generation β1-blocker, synergistically increased the sensitivity of BT-474 breast cancer cells to the potent and selective FGFR inhibitors erdafitinib (JNJ-42756493) and AZD4547. A combination of nebivolol and erdafitinib markedly reduced AKT activation. Suppression of AKT activation using specific siRNA and a selective inhibitor further enhanced cell sensitivity to combined treatment with nebivolol and erdafitinib, whereas SC79, a potent activator of AKT, reduced cell sensitivity to nebivolol and erdafitinib. Conclusion: Enhanced sensitivity of BT-474 breast cancer cells to nebivolol and erdafitinib was probably associated with down-regulation of AKT activation. Combined treatment with nebivolol and erdafitinib is a promising strategy for breast cancer treatment.

Key Words:
  • AKT
  • breast cancer
  • combination therapy
  • FGFR
  • nebivolol
  • Received February 1, 2023.
  • Revision received March 7, 2023.
  • Accepted March 8, 2023.
  • Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 43 (5)
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Nebivolol Sensitizes BT-474 Breast Cancer Cells to FGFR Inhibitors
YU JIN KIM, SE-KYEONG JANG, GYEONGMI KIM, SUNG-EUN HONG, CHAN SUB PARK, MIN-KI SEONG, HYUN-AH KIM, KWANG SEOK KIM, CHUN-HO KIM, KI SOO PARK, JUNGIL HONG, HYEON-OK JIN, IN-CHUL PARK
Anticancer Research May 2023, 43 (5) 1973-1980; DOI: 10.21873/anticanres.16357

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Nebivolol Sensitizes BT-474 Breast Cancer Cells to FGFR Inhibitors
YU JIN KIM, SE-KYEONG JANG, GYEONGMI KIM, SUNG-EUN HONG, CHAN SUB PARK, MIN-KI SEONG, HYUN-AH KIM, KWANG SEOK KIM, CHUN-HO KIM, KI SOO PARK, JUNGIL HONG, HYEON-OK JIN, IN-CHUL PARK
Anticancer Research May 2023, 43 (5) 1973-1980; DOI: 10.21873/anticanres.16357
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