热疗对纤维肉瘤S180株的抑瘤作用及其生物学机制

The study of the therapeutic effect and molecular mechanisms of hyperthermia on the S-180 tumor cell line

目的探讨热疗对纤维肉瘤S180株的抑瘤作用及其生物学机制。方法实验用40只昆明小鼠,接种S180肿瘤细胞株后用加热进行实验干预,标本于实验后6、20、54h取材,原位末断标记法(TUNEL)检测凋亡细胞,流式细胞仪测定细胞周期分布,RT-PCR检测Bcl-2基因的mRNA表达。结果热疗可以诱导纤维肉瘤S180株细胞凋亡,改变细胞周期分布,使发生G1期阻滞,下调Bcl-2基因。结论热疗对纤维肉瘤S180株有抑瘤作用,本实验结果为进一步开展基因配合热放疗治疗肿瘤和选择肿瘤放化疗结合时机和化疗药物提供了实验依据。

Objective Fibrosarcomas of the bone is an locally aggressive lesions with a metastatic potential. Surgery and radiation therapy are standard treatments with poor prognostic outcome. New methods are needed to improve the treatment outcome. Hyperthermia which utilizes heat effects to kill tumor cells can be an adjuvant therapy for radiotherapy. This study is to investigate the hyperthermia therapeutic effect and biology mechanism on fibrosarcoma cell line S-180. Methods S-180 tumor xenografts were grown in Kunming mice. The experiment was divided into two groups in random： contrast and hyperthermia. The mice were treated with hyperthermia at 42.5 C for 30 minutes. 6, 20, 54 hours after the treatment, xenografts were harvested followed by a series of analysis. Hyperthermia-induced apoptosis was measured by TUNEL staining. Cell cycle redistribution was measured by flow-cytometry analysis. Transcription of Bcl-2 mRNA is measured by RT-PCR analysis. Results 30-minutes hyperthermia induces cell cycle arrest at the G1 phase. Hyperthermia can induce apoptosis, bcl-2 mRNA level after hyperthermia is lowered （P〈0.01）. Conclusions Hyperthermia can induce cell cycle arrest and apopotosis in coordinated with down regulation of BCL-2 transcription. These suggest that hyperthermia can be an efficient treatment for fibrosarcoma of the bone. This also gives implications on that： if hyperthermia can be combined with radiotherapy, it may increase the effect of radiotherapy.