咪喹莫特抑制小鼠体表黑色素瘤生长和促使肿瘤特异性放疗增敏的实验研究

Effects of imiquimod on the growth inhibition of B16F10 melanoma cells and induces tumor-specific radiosensitivity in C57BL/6 mice model

关键词:  咪喹莫特  黑色素瘤模型  放疗增敏  微管相关蛋白1轻链3B  α-平滑肌激动蛋白

Key words:  [Key words]　IMQ  melanoma model  radiosensitivity  MAP1LC3B  α-SMA

摘要:

[摘要]　目的　研究咪喹莫特联合外放疗对C57BL/6小鼠黑色素瘤模型肿瘤生长的影响，并判定咪喹莫特对肿瘤特异性放疗增敏的疗效。　方法　建立C57BL/6小鼠(n=20)的体表黑色素瘤模型，随机分为对照组、放疗组、咪喹莫特治疗组和放疗联合咪喹莫特治疗组。测量肿瘤生长体积，观察肿瘤生长延迟效应，并采用免疫组织化学检测和生存曲线评估咪喹莫特对肿瘤放疗增敏效果。　结果　放疗联合咪喹莫特治疗组肿瘤生长延迟最显著，其次治疗效果依次为咪喹莫特治疗组、放疗组和对照组。4组间两两比较，差异均有显著性意义(P<0.01)。C57BL/6小鼠黑色素瘤的组织病理学检测中，发现微管相关蛋白1轻链3B(MAP1LC3B)和α-平滑肌激动蛋白(α-SMA)在放疗联合咪喹莫特治疗组呈高表达。3种不同治疗组的MAP1LC3B和α-SMA表达与对照组间比较，差异均有显著性意义 (P<0.05)。C57BL/6小鼠生存表证实，放疗联合咪喹莫特治疗组生存率明显优于其他治疗组和对照组，差异有显著性意义(P<0.05)。　结论　咪喹莫特联合外放疗对C57BL/6小鼠黑色素瘤生长有绝对延迟效应，咪喹莫特可为新的肿瘤特异性放疗增敏诱导剂。

Abstract:

[Abstract] Objective　To investigate the tumor-specific radiosensitivity of B16F10 melanoma cells with imiquimod combines with or without irradiation,and to determine the effects on the tumor growth of localized melanoma model in C57BL/6 mice.　Methods　B16F10 melanoma cells were injected subcutaneously into the right hind axilla of C57BL/6 mice by othotopic implantation to establish the localized melanoma model. The tumor-bearing C57BL/6 mice were randomized into 4 groups,control group,radiation group (RT group),intra-tumoral injection of imiquimod group (IMQ group),and RT combined with IMQ group (RT+IMQ group). When tumor volume was measuring longest and shortest diameter,the tumor growth curve was observed at various times after injection and/or irradiation in tumor-bearing C57BL/6 mice. The effect of treatment was assessed by tumor growth delay. The effects of tumor radiosensitivity were evaluated using anti-LC3B and α-SMA immunohistochemistry in melanoma tissues,and analyzed the C57BL/6 mice survival.　Results　The delay of tumor growth was highest in the group which received treatment of RT+IMQ,the second highest was the group which only received treatment of IMQ,the third is the group which only received treatment of RT,and the last is the group which received control (P<0.05). Expression of microtubule-associate protein 1 light chain 3B (MAP1LC3B) and alpha smooth muscle actin (α-SMA) protein was marked histopathological difference of C57BL/6 mice of localized melanoma tissues between RT+IMQ group and control group，and difference was statistically significant (P<0.05). Life tables showed that RT+IMQ group is inversely correlated with overall survival of C57BL/6 mice with localized melanoma model(P<0.05). Conclusions　These results suggest that imiquimod combined with irradiation would be promoted absolute tumor growth delay in C57BL/6 mice of localized melanoma model,and imiquimod may be a novel tumor-specific radioseccitivity of inducer for