Jie Liu
Central South University, China.
Title: The mechanism of β-blockers on breast cancer proliferation and the influence of ADRB2 polymorphisms on β-blockers’ anti-proliferation
Biography
Biography: Jie Liu
Abstract
β-blockers are regular drugs used for cardiovascular diseases. However, increasing studies proposed that β-blockers could be potential anti-cancer drugs, especially for breast cancer, which could significantly improve patients’ survival. β adrenergic receptors are important drug target and polymorphisms in ADRB2 might affect individual-difference. We studied the mechanism of β-blockers in MDA-MB-231 proliferation and focused on four haplotypes comprised by R16G and Q27E of ADRB2 to discover their influence on β-blockers’ anti-proliferation in HEK293. AlarmBlue assay was used to measure cell viability and propranolol and ICI118,551 reduced cell viability by concentration dependently, and have better effect than metoprolol in MDA-MB-231 (p<0.05); flow cytometry assay was used to detect cell cycle distribution and propranolol (200μM) and ICI118,551 (150μM) could cause G1/S phase arrest compared to control(propranolol: G1 54.9±5.3%, S 15.1±2.3%; ICI118,551: G1 61.7±2.9%, S 11.5±6.6%; control: G1 45.8±1.0%, S 23.7±2.4%) (p<0.05); propranolol and ICI118,551 were also observed to lower the expression of p-ERK, p-p38 and COX-2 in MDA-MB-231. Four plasmids were transfected into HEK293. Q-PCR was used to detect mRNA level of ADRB2 and R16Q27 haplotype had higher expression level than others (p<0.05). MTS assay was used to measure cell viability and there is no difference between four haplotypes (p>0.05); further treated with ICI118,551 for 24h, R16Q27 haplotype have lower cell viability (p<0.05) and lower expression of p-ERK and COX-2 (ICI118,551: 80μM). β-blockers inhibited breast cancer cell proliferation might be related to MAPK /COX-2 pathway; R16Q27 haplotype had better drug response, offering genetic guidance for clinic therapy.