The adrenergic receptor antagonists propranolol and carvedilol decrease bone sarcoma cell viability and sustained carvedilol reduces clonogenic survival and increases radiosensitivity in canine osteosarcoma cells

Adrenergic receptor (AR) expression has been demonstrated at several sites of primary and metastatic tumour growth and may influence proliferation, survival, metastasis and angiogenesis. AR antagonists like propranolol and carvedilol inhibit proliferation, induce apoptosis and synergize with chemotherapy agents in some cancers. Radiation resistance is mediated in many cells by upregulation of pro‐survival pathways, which may be influenced by ARs. Studies evaluating AR antagonists combined with radiation are limited. The purpose of this study was to determine the effect of propranolol and carvedilol on viability and radiosensitivity in sarcoma cell lines. The hypothesis was that propranolol and carvedilol would increase radiosensitivity in four primary bone sarcoma cell lines. Single agent propranolol or carvedilol inhibited cell viability in all cell lines in a concentration‐dependent manner. The mean inhibitory concentrations (IC₅₀) for carvedilol were approximately 4‐fold lower than propranolol and may be clinically relevant in vivo. Immunoblot analysis confirmed AR expression in both human and canine sarcoma cell lines; however, there was no correlation between baseline AR protein expression and radiosensitivity. Short duration treatment with carvedilol and propranolol did not significantly affect clonogenic survival. Prolonged exposure to propranolol and carvedilol significantly decreased the surviving fraction of canine osteosarcoma cells after 3Gy radiation. Based on our results and possible in vivo activity in dogs, further studies investigating the effects of carvedilol on sarcoma are warranted.     

卡维地洛治疗老年糖尿病合并慢性心力衰竭的临床疗效和安全性观察

目的观察卡维地洛治疗老年2型糖尿病并慢性心力衰竭患者的疗效及安全性。方法老年2型糖尿病合并慢性心力衰竭患者73例随机分为卡维地洛组45例和对照组28例。对照组采用常规治疗,卡维地洛组在常规治疗基础上加服卡维地洛3.125mg,2次/d,每2周递增直至靶剂量(25mg,2次/d)或最大耐受剂量。随访12个月,比较治疗后两组患者的心率、血压、心脏功能以及血糖、胆固醇等变化,心脏事件以及药物耐受性。结果(1)随访12个月后,卡维地洛组死亡2例、中断卡维地洛2例,对照组死亡4例,均予剔除;(2)治疗后卡维地洛组(41例)心脏功能LVEDD、LVESD及LVEF较对照组(24例)改善明显(P<0.05),心率低于对照组(P<0.01),但2组心率均在正常范围内;随访期间,卡维地洛组心脏事件总发生率低于对照组(7/45vs12/28),差异有统计学意义(P<0.01);(3)两组均未发生低血糖反应、水肿及高度房室传导阻滞,两组患者的血压、血清钠、血清肌酐清除率、空腹血糖、糖化血红蛋白、低密度胆固醇等差异无统计学意义(P>0.05)。结论卡维地洛在老年糖尿病并心力衰竭患者治疗中具有良好的安全性和有效性,能改善患者的心脏功能,降低心脏事件发生,对血糖、血脂代谢没有明显影响。