联用冷冻疗法和化疗药物诱导人胃癌细胞系凋亡

Optimization and induction of apoptosis in combination cryotherapy and chemotherapy in human stomach cancer xenografts in SCID mice

目的:探索冷冻与化疗药物联合使用对实体肿瘤细胞凋亡的影响。方法:裸鼠接种人胃癌细胞系SGC-7901,成瘤后联用冷冻疗法(氧化亚氮,N2O)和化疗药物顺铂(Cis-platinum,Cisp)治疗。结果:冷冻和Cisp同时应用与单独冷冻疗法相比并无明显优势,而两种疗法间隔应用可明显减小肿瘤体积,应用先后顺序没有差别,但间隔48 h应用的效果都优于间隔24 h。当先应用Cisp,48 h后冷冻治疗时肿瘤内凋亡细胞数量明显增加,且凋亡水平与肿瘤细胞内促凋亡基因Puma、Noxa和Bim的mRNA表达水平升高相关,而抑制凋亡基因Bax和Bcl-2的mRNA表达水平无明显改变,只有Mcl-1的表达水平轻微增加。结论:间隔48 h先后应用化疗和冷冻与其他疗法相比,可以更有效地促进肿瘤凋亡。

Aim：The aim was to investigate whether combination of cryotherapy（nitrous oxide） with chemotherapy（Cis-platinum,Cisp） could suppress the development of human gastric cancer cell line SGC-7901 in vivo. Methods： Nude mice injected with doxorubicin-resistant SGC-7901 cells（107）,assigned into eight groups of three mice each,challenged with the optimal parameters for combination of cryotherapy（nitrous oxide） with chemotherapy（Cis-platinum,Cisp） and characterised some of the signals involved for apoptosis activation. Results： No advantage appeared when cryotherapy and Cisp were combined simultaneously compared with cryosurgery alone.In contrast,tumour volumes were reduced after a sequential treatment schedule.The sequence of treatment had no impact on the observed tumour growth inhibition in mice,and significant benefit appeared when the sequential treatment was separated by 48 h.The number of apoptotic cells was significantly augmented in the sequential treatment schedule where Cisp was administered 48 h before cryotherapy.In this sequential treatment,the number of apoptotic cells correlated with heightened expression of the Puma,Noxa and Bim at the mRNA level.No significant change in Bax and Bcl-2 mRNA expression was apparent,whereas Mcl-1 expression increased slightly. Conclusion：Data indicate that 48 h sequential rather than simultaneous cryotherapy with Cisp.