慢性应激对肿瘤术后复发和转移的影响及机制探讨

Recurrance and distant metastasis are the chief drivers of breast cancer-related mortality. Recent researches reported, in clinic, propranolol obviously reduced the incidences of local recurrance and distant metastasis, also prolonged breast cancer specifc survival, distant metastasis-free interval and disease free interval. Propranolol exhibited better disease free survival in clinical research of triple negative breast cancer. It could be stated that tumor patients bearing chronic stress encountered the tension of ‘cancer’, induced the increase of releasing stress-related hormones(SRH), activitated signal transducer and activator of transcription 3(STAT3) by the pathway of β-adrenergic receptor(β-AR), upregulated the secretions of cyclinD1, VEGF anf MMPs in tumor parenchymal cells and stromal tumor-associated macrophages promoting the proliferation, migration, invasion of tumor cells and tumor angiogenisis, which could be blocked byβ-AR antagonists: propranolol. This research will adpot the different mouse mold following tumor resection from convention imitaing the microenviroment in vivo after surgury of tumor patients as maximal as possible. Two disperate stress models will be taken to demonstrate the impact of chronic stress on recurrance and metastasis of tumors. Time to date, homologous reprot hasn’t been emerged at home and abroad.

复发和远处转移是恶性肿瘤致死的根本原因。研究报道β肾上腺素能受体拮抗剂普萘洛尔明显降低了乳腺癌术后的局部复发率和远处转移率，延长了乳腺癌相关生存时间、无远处转移间隔和无疾病间隔。在对三阴性乳腺癌的临床研究中普萘洛尔同样显示了更好的无病生存优势。肿瘤患者术后仍然面临“癌症”的压力，处于慢性应激状态，导致压力相关激素的释放增加，通过β肾上腺素能受体途径，激活信号转导和转录激活因子3（STAT3），促使肿瘤实质细胞本身和间质中的肿瘤相关巨噬细胞分泌细胞周期蛋白（cyclin D1）、血管内皮生长因子（VEGF）、基质金属蛋白酶（MMP）等表达，发挥促细胞增殖、迁徙、侵袭和促肿瘤血管生成等作用，而这些效应可以被β肾上腺素能受体拮抗剂普萘洛尔所阻断。本研究拟采用有别于常规的小鼠肿瘤切除术后模型，最大程度地模拟肿瘤患者术后的体内微环境，术后应用两种不同的应激模式以充分论证慢性应激对肿瘤复发和转移的影响

复发和远处转移是恶性肿瘤致死的主要根本原因。新近的研究报道，普萘洛尔在临床上明显降低了乳腺癌术后的局部复发率和远处转移率，延长了乳腺癌相关生存时间、无远处转移间隔和无疾病间隔时间。在对三阴性乳腺癌的临床研究中普萘洛尔同样显示了更好的无病生存优势。肿瘤患者术后仍然面临“癌症”的压力，处于慢性应激状态，导致压力相关激素的释放增加，通过β肾上腺素能受体途径，激活信号转导和转录激活因子3，促使肿瘤实质细胞本身和间质中的肿瘤相关巨噬细胞分泌细胞周期蛋白（cyclin D1）、血管内皮生长因子（VEGF）、基质金属蛋白酶（MMP）等表达，发挥促细胞增殖、迁徙、侵袭和促肿瘤血管生成等作用，而这些效应可以被β肾上腺素能受体拮抗剂：普萘洛尔所阻断。本研究拟采用有别于常规的小鼠肿瘤切除术后模型，最大程度地模拟肿瘤患者术后的体内微环境，术后应用两种不同的应激模式（物理和化学模式）以充分论证慢性应激对肿瘤复发和转移的影响。我们希望通过对该课题的研究，为临床防治肿瘤患者术后复发和转移提供新的策略，延长患者的生存期。