低温等离子体联合X射线照射对人肝癌裸鼠肿瘤模型的生物学效应

doi:10.3760/cma.j.issn.1673422X.2017.04.004

摘要/Abstract

摘要： 目的探讨低温等离子体（NTP）联合X射线照射对人肝癌荷瘤裸鼠的生物学效应。方法通过皮下接种，建立人肝癌HepG2裸鼠肿瘤模型，分为对照组、NTP治疗组、X射线照射组、联合治疗组。应用苏木精伊红（HE）染色观察肿瘤微环境改变；应用原位末端转移酶标记技术（TUNEL）测定肿瘤组织内细胞凋亡水平；应用免疫组织化学法检测基质金属蛋白酶2（MMP2）表达情况；应用透射电镜观察细胞器结构改变。结果对照组、NTP治疗组、X射线照射组、联合治疗组终末肿瘤体积分别为（543.96±108.45）、（436.54±65.49）、（351.66±56.68）、（281.97±35.60）mm3，4组比较差异具有统计学意义（F=9.63，P=0.01），X射线照射组与联合治疗组之间差异具有统计学意义（P=0.05）。HE染色显示联合治疗组较其余各组出现的坏死区域面积更大。TUNEL法显示4组凋亡指数分别为（0.95±0.13）%、（5.82±0.26）%、（7.53±0.43）%、（11.07±0.35）%，4组间差异具有统计学意义（F=547.76，P=0.00），且X射线照射组与NTP治疗组之间差异具有统计学意义（P=0.00）。免疫组织化学显示4组免疫反应评分分别为12、9、9、2。电镜下观察发现联合治疗组较其余各组出现更多凋亡小体，并伴随线粒体水肿。结论 NTP和X射线照射在治疗人肝癌荷瘤裸鼠模型上具有协同作用，为恶性肿瘤提供了一种新的可能治疗方案。

关键词: 放射疗法, 肝肿瘤, 低温等离子体

Abstract: Objective To investigate the biological effects of nonthermal plasma (NTP) combined with X-ray irradiation on human hepatocellular carcinoma in nude mice. Methods By subcutaneous inoculation, tumor models of human hepatocellular carcinoma HepG2 in nude mice were established, and these mice were divided into control group, NTP treatment group, X-ray irradiation group, combined treatment group. The changes of tumor microenvironment were observed using hematoxylineosin (HE) staining. The terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) was used to determine the level of neuronal apoptosis in tumor tissues. The expression of metal matrix proteinase-2 (MMP-2) was detected by immunohistochemical assay. Transmission electron microscope was used to observe cell structure changes. Results The final tumor volumes of control group, NTP treatment group, X-ray irradiation group, combined treatment group were (543.96±108.45), (436.54±65.49), (351.66±56.68), (281.97±35.60)mm3, with a statistically significant difference (F=9.63, P=0.01), and the difference between X-ray radiation group and the combination treatment group was significant (P=0.05). HE staining showed that there was a larger area of necrosis in the combined treatment group compared with the other groups. TUNEL showed that the apoptotic indexes were (0.95±0.13)%, (5.82±0.26)%, (7.53±0.43)%, (11.07±0.35)% respectively, with a statistically significant difference (F=547.76, P=0.00), and the difference between X-ray radiation group and the combination treatment group was statistically significant (P=0.00). The immune scores of each group were 12, 9, 9, 2. Electron microscopic observation showed that there were more apoptotic bodies in the combined treatment group than those in the other groups, accompanied by mitochondrial edema. Conclusion NTP and X-ray irradiation therapy in the treatment of human hepatocellular carcinoma in nude mice model has a synergistic effect. Probably, it can be a new type of treatment in curing cancers.

Key words: Radiotherapy, Liver neoplasms, Nonthermal plasma

陈辰,周菊英. 低温等离子体联合X射线照射对人肝癌裸鼠肿瘤模型的生物学效应[J]. 国际肿瘤学杂志, 2017, 44(4): 257-261.

Chen Chen, Zhou Juying. Biological effects of nonthermal plasma combined with Xray irradiation on human hepatocellular carcinoma in nude mice[J]. Journal of International Oncology, 2017, 44(4): 257-261.

参考文献

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