石墨烯发热膜的抑瘤作用初探

目的:初步探讨石墨烯发热膜的抗肿瘤作用。方法:体外使用96孔平底板培养对数期生长的CCD-1095SK、MCF-7、A375和B16-F10细胞，使用石墨烯发热膜或温箱在不同温度（37 ℃、40 ℃、41.5 ℃、43 ℃）下恒温处理1小时，继续培养24小时后检测细胞生存率。体内接种黑色素瘤细胞株B16-F10于6~8周龄C57BL/6小鼠和裸鼠，C57BL/6小鼠使用石墨烯发热膜处理（38.5 ℃、39.5 ℃和40.5 ℃，30分钟/次，2次/天），同时给予达卡巴嗪（dacarbazine，DTIC）80 mg/kg或PBS作为控制,每两天测量一次肿瘤体积并记录小鼠的体重和生存状况，接种后第21天处死小鼠剥离瘤体，称重，多聚甲醛固定后进行HE染色。裸鼠使用石墨烯发热膜处理（37 ℃、38.5 ℃和40 ℃，30分钟/次，2次/天），每两天测量一次肿瘤体积并记录生存状况。结果:体外石墨烯发热膜处理达到40 ℃时，对MCF-7和A375细胞增殖具有抑制作用，但对于CCD-1095SK和B16-F10细胞，需要达到41.5 ℃才具有增殖抑制作用。在免疫健全的C57BL/6小鼠模型中，石墨烯发热膜40.5 ℃处理组肿瘤体积较控制组减小，石墨烯发热膜40.5 ℃处理和DTIC联用组的肿瘤体积较单独处理组减小。对于免疫不全裸鼠肿瘤模型，石墨烯发热膜处理未能减小肿瘤体积，也未能延长小鼠的生存期。结论:体外石墨烯发热膜处理具有抑制肿瘤细胞增殖的作用，体内联合DTIC和石墨烯发热膜处理具有抑制B16-F10肿瘤模型生长的作用，其机制有可能是间接增强了抗肿瘤免疫应答。

Preliminary study on the antitumor effect of graphene heating film

Objective:To preliminarily discuss the antitumor effect of graphene heating film.Methods:CCD-1095SK,MCF-7,A375 and B16-F10 cells were cultured in a 96-well flat plate in vitro and treated at different temperatures (37 ℃,40 ℃,41.5 ℃,43 ℃) for 1 hour using a graphene heating film or a temperature chamber.Cell survival was measured after 24 hours of continuous culture.C57BL/6 mice and nude mice aged 6~8 weeks were inoculated with mouse melanoma cell line B16-F10.C57BL/6 mice were treated with graphene heating film (38.5 ℃,39.5 ℃ and 40.5 ℃,30 min/time,twice/day),with or without dacarbazine (DTIC,80 mg/kg) or PBS was given as control.Tumor volume was measured every two days.The body weight and survival rates were recorded.On the 21st day after inoculation,the mice were sacrificed for tumor dissection,weighed,fixed with paraformaldehyde and stained with HE.Nude mice were treated with graphene heating film (37 ℃,38.5 ℃ and 40 ℃,30 min/time,twice/day).Tumor volume was measured every two days and survival was recorded.Results:The proliferation of MCF-7 and A375 cells was inhibited at 40 ℃,but the proliferation of CCD-1095SK and B16-F10 cells was inhibited only at 41.5 ℃.In the C57BL/6 mouse model,the tumor volume in the 40.5 ℃ treatment group was decreased compared with the control group,and the tumor volume in the 40.5 ℃ treatment group combined with DTIC was decreased compared with the single treatment group.In the immunocompromised nude mouse tumor model,the graphene heating film treatment did not reduce the tumor volume or prolong the survival time of the mice.Conclusion:In vitro graphene heating film treatment can inhibit the proliferation of tumor cells,and in vivo DTIC and graphene heating film treatment can inhibit the growth of B16-F10 tumor model.The mechanism may be indirectly enhanced anti-tumor immune response.