PT  - JOURNAL ARTICLE
AU  - KIM, YU JIN
AU  - JANG, SE-KYEONG
AU  - KIM, GYEONGMI
AU  - HONG, SUNG-EUN
AU  - PARK, CHAN SUB
AU  - SEONG, MIN-KI
AU  - KIM, HYUN-AH
AU  - KIM, KWANG SEOK
AU  - KIM, CHUN-HO
AU  - PARK, KI SOO
AU  - HONG, JUNGIL
AU  - JIN, HYEON-OK
AU  - PARK, IN-CHUL
TI  - Nebivolol Sensitizes BT-474 Breast Cancer Cells to FGFR Inhibitors
AID  - 10.21873/anticanres.16357
DP  - 2023 May 01
TA  - Anticancer Research
PG  - 1973--1980
VI  - 43
IP  - 5
4099  - http://ar.iiarjournals.org/content/43/5/1973.short
4100  - http://ar.iiarjournals.org/content/43/5/1973.full
SO  - Anticancer Res2023 May 01; 43
AB  - 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.