Suppression of human pancreatic cancer cell proliferation by β-adrenoceptor antagonists via induction of apoptosis in vitro

Objective: To observe whether β-adrenoceptor antagonists can produce inhibitory effects by inducing apoptosis of pancreatic cancer (PC-2) cells. Methods: The β₁-adrenoceptor antagonist metoprolol, β-adrenoceptor antagonist propranolol and β₂-adrenoceptor antagonist butoxamine were used to induce apoptosis in PC-2 cells. The mRNA and protein expressions of β₁-and β₁-adrenoceptors were analyzed by RT-PCR and Western blotting. The apoptosis index was determined by Hoechst 33342 fluorescent staining, TUNEL and Annexin V and FITC/PI FCM assay. The expressions of Caspase-3, Caspase-9 and Caspase-8 were analyzed by Western blotting. Results: PC-2 cell line expressed mRNA and protein for both of β₁- and β₂-adrenoceptors. The Hoechst staining, TUNEL and FCM assay showed that the three drugs increased the number of apoptotic cells; TUNEL assay indicated that the rate of apoptosis was the highest using butoxamine (15.4 ± 1.99)% followed by propranolol (11.25 ± 1.95)%, while the least was using metoprolol (7.62 ± 1.46)%. FCM assay showed that the rate of apoptosis was the highest using butoxamine (16.2 ± 1.58)%, followed by propranolol (14.7 ± 1.96)%, while the least was using metoprolol (6.29 ± 1.77)%. β-adrenoceptor antagonist therapy affected Caspase-3 and Caspase-9 fragment expression, but not Caspase-8. Conclusion: It is suggested that β-adrenoceptor antagonists induce apoptosis of PC-2 cells through inhibiting β₂-adrenergic receptor mainly.