RT Journal Article
SR Electronic
T1 Nebivolol Sensitizes BT-474 Breast Cancer Cells to FGFR Inhibitors
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 1973
OP 1980
DO 10.21873/anticanres.16357
VO 43
IS 5
A1 KIM, YU JIN
A1 JANG, SE-KYEONG
A1 KIM, GYEONGMI
A1 HONG, SUNG-EUN
A1 PARK, CHAN SUB
A1 SEONG, MIN-KI
A1 KIM, HYUN-AH
A1 KIM, KWANG SEOK
A1 KIM, CHUN-HO
A1 PARK, KI SOO
A1 HONG, JUNGIL
A1 JIN, HYEON-OK
A1 PARK, IN-CHUL
YR 2023
UL http://ar.iiarjournals.org/content/43/5/1973.abstract
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.