塞来昔布联合运动干预对人结肠癌小鼠移植瘤的影响及其机制

Effect and mechanism of celecoxib combined with exercise on inhibiting the development of transplanted human colon cancer tumors in mice

目的探讨塞来昔布联合运动干预对人结肠癌小鼠移植瘤血管生成的影响及其机制。方法将HT-29细胞株诱导的人结肠癌小鼠皮下移植瘤模型随机分为A组和B组,每组再随机分为肿瘤对照组、跑台运动组、塞来昔布组和跑台运动+塞来昔布组。分别给予塞来昔布灌胃和(或)跑台运动干预。A组干预期间记录小鼠的死亡时间,用于生存分析。B组5周干预结束后收集静脉血和移植瘤组织,测定血清转化生长因子-β1(TGF-β1)、血管内皮生长因子(VEGF)水平、组织CD105标记的肿瘤微血管密度(MVD)计数以及移植瘤体积,分析各组小鼠移植瘤体积和血管生成相关因子变化情况。结果跑台运动+塞来昔布组的生存率明显高于肿瘤对照组(P<0.01),移植瘤体积明显低于肿瘤对照组、跑台运动组、塞来昔布组(P<0.05或P<0.01),血清TGF-β1、VEGF水平、组织CD105标记的MVD计数均明显低于肿瘤对照组、跑台运动组、塞来昔布组(P<0.05或P<0.01)。肿瘤对照组血清TGF-β1、VEGF与CD105标记的MVD呈正相关(P<0.05或P<0.01)。结论塞来昔布联合运动干预能够抑制人结肠癌小鼠移植瘤的发生发展,效果优于单一的塞来昔布治疗或运动干预,可显著提高小鼠生存率。在抑制TGF-β1、VEGF、CD105标记的MVD抗新血管形成方面,塞来昔布治疗和运动干预可能存在协同效应。塞来昔布联合运动干预可能是一种有效的结肠癌防治策略。

Objective To explore the effect and mechanism of celecoxib combined with exercise on angiogenesis in mice with transplanted human colon cancer and provide new insights into the clinical prevention and treatment of colorectal cancer.Methods Mice with a human colon cancer tumor model induced by subcutaneous transplantation of HT-29 cells were randomly divided into group A and group B.Mice in each group were randomly divided into tumor control,treadmill,celecoxib and treadmill+celecoxib groups.The time of death for group A was recorded for survival analysis.After 5 weeks of intervention,venous blood and transplanted tumor tissue were collected from mice in group B,and serum TGF-β1 and VEGF levels were measured.Changes in tumor volume and angiogenesis-related factors were analyzed based on CD105-labeled MVD count and tumor volume change in each group.Results The survival rate in the treadmill+celecoxib group was significantly higher than that in control group(P<0.01).Moreover,the tumor volume in the treadmill+celecoxib group was significantly lower than those in the tumor control,treadmill and celecoxib groups(P<0.05 or P<0.01).Serum levels of TGF-β1 and VEGF were significantly lower in the treadmill+celecoxib group than in the tumor control,treadmill and celecoxib groups(P<0.05 or P<0.01).Serum TGF-β1 and VEGF were correlated with CD105-labeled MVD in the tumor control group(P<0.05 or P<0.01).Conclusion Celecoxib treatment combined with exercise can inhibit the occurrence and development of transplanted human colon cancer tumors in mice,and its effect is better than that of celecoxib therapy or exercise alone.It can significantly improve the survival rate of mice and inhibit TGF-β1 and VEGF.Celecoxib therapy combined with exercise may have synergistic effects on anti-angiogenesis and CD105-labeled MVD.Celecoxib treatment combined with exercise may be an effective strategy for the prevention and treatment of colon cancer.