摘要
目的:研究情绪因素以及通过药物控制情绪因素对肿瘤休眠状态的维持与打破及后续复发转移的影响。方法:利用肿瘤休眠模型,附加单笼饲养和不定时空瓶刺激联合诱导小鼠产生焦虑、愤怒等应激情绪的小鼠慢性情绪应激模型。通过灌胃给予常规抗焦虑药物地西泮来控制焦虑情绪,探讨情绪及抗焦虑药物对肿瘤休眠状态的维持及防止肿瘤复发的作用。实验分为五组,分别为休眠对照组、单纯给药组、诱导焦虑组、焦虑给药组和外伤刺激组。以500个小鼠乳腺癌细胞Ca761-03接种于小鼠左腿肌肉。休眠对照组、单纯给药组和外伤刺激组常规饲养,其中外伤刺激组在第1个月末切除右爪作为外伤刺激,单纯给药组每天定量灌胃给予地西泮溶液。诱导焦虑组和焦虑给药组以单笼饲养和不定时空瓶刺激联合诱导小鼠产生焦虑、愤怒等应激情绪,其中焦虑给药组每天定量灌胃给予地西泮溶液。连续观察2个月,观察小鼠焦虑情况,观察肿瘤休眠打破(肿瘤发生)及肿瘤转移发生情况。结果:各组肿瘤休眠率分别为70%、100%、60%、90%和40%。各组成瘤率分别为30%、0、40%、10%和60%。各组的肺转移率分别为20%、0、30%、0和60%。结论:本项研究结果证实,长期负面情绪会促进肿瘤休眠状态的打破,加速肿瘤的生长、复发及转移。抗焦虑药物可以明显减少焦虑行为,并有利于肿瘤休眠状态的维持,减少肿瘤的复发。
Objective: To investigate the effects of psychological stress and anti-anxiety drugs on tumor dormancy, relapse and metastasis. Methods: Isolation-stress and stochastic empty bottle were combined to establish mice model of chronic emotional stress, and routine anti-anxiety drug Diazepam was used to control the anxi- ety. The experimental animals included 5 groups: the dormancy control group, the anti-anxiety drug group, the group with induced anxiety, the group with induced anxiety and anti-anxiety drug, and the trauma group. Tumor dormant status was established by inoculation of 500 ca761-03 cells into the left leg muscle of the mice. Besides isolated caging and stochastic empty bottle, Diazepam was orally delivered twice daily in the drug group and the group with induced anxiety and anti-anxiety drug. The trauma group was given traumatic stimulation at the end of the first month. All animals were continuously observed for 2 months. Tissues at the site of injection of tumor cells, lungs and lymph nodes were dissected, fixed, embedded and sectioned. H&E staining was used to observe the tumor occurrence and metastasis. Results: At the end of the second month, the dormancy rates were 70%, 100%, 40%, 90% and 40%, respectively, in the five groups. The tumorigenecity rates were 30%, 0%, 40%, 10% and 60%, respectively. And the lung metastasis rates of each group were 20%, 0%, 30%, 0% and 60%, respectively. Conclusion: Negative emotion can stimulate the breakthrough of tumor dormancy and promote the growth and spread of tumor cells. Anti-anxiety drug can obviously reduce the anxious emotion and tumor occurrence. The anti-anxiety therapy is helpful for the maintenance of dormant status and preventing tumor relapse.
出处
《中国肿瘤临床》
CAS
CSCD
北大核心
2008年第23期1369-1372,共4页
Chinese Journal of Clinical Oncology
基金
国家科技部973项目基金资助(编号:2002CB513100-2)~~
关键词
肿瘤休眠
情绪因素
抗焦虑药物
复发
转移
Tumor dormancy
Psychological stress
Anti-anxiety drugs
Relapse
Metastasis