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.

中文翻译：

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肾上腺素能受体拮抗剂普萘洛尔和卡维地洛降低了骨肉瘤细胞的活力，持续的卡维地洛降低了犬骨肉瘤细胞的克隆形成存活率并增加了放射敏感性。

肾上腺素能受体（AR）的表达已在原发性和转移性肿瘤生长的多个部位得到证实，并可能影响增殖，存活，转移和血管生成。在某些癌症中，如心得安和卡维地洛等AR拮抗剂可抑制增殖，诱导凋亡并与化疗药物协同作用。辐射抗性是通过上调生存途径来介导的，这可能受AR的影响。评价AR拮抗剂与放射线结合的研究是有限的。这项研究的目的是确定普萘洛尔和卡维地洛对肉瘤细胞系活力和放射敏感性的影响。假设是普萘洛尔和卡维地洛将增加四种原发性骨肉瘤细胞系的放射敏感性。单药普萘洛尔或卡维地洛以浓度依赖的方式抑制所有细胞系的细胞活力。平均抑制浓度（IC卡维地洛的₅₀）比普萘洛尔低约4倍，并且在体内可能与临床有关。免疫印迹分析证实了AR在人和犬肉瘤细胞系中的表达；然而，基线AR蛋白表达与放射敏感性之间没有相关性。卡维地洛和普萘洛尔的短期治疗不会显着影响克隆形成存活。长时间暴露于心得安和卡维地洛可显着降低3Gy辐射后犬骨肉瘤细胞的存活率。根据我们的研究结果和可能的犬体内活性，有必要进一步研究卡维地洛对肉瘤的影响。