| 吴清华,何玉洁,顾琛,姜建威.153Sm-DTPA-c(CGRRAGGSC)对人MHCC97-H肝癌裸鼠模型的抑瘤作用[J].中华放射医学与防护杂志,2015,35(2):92-97 |
| 153Sm-DTPA-c(CGRRAGGSC)对人MHCC97-H肝癌裸鼠模型的抑瘤作用 |
| Anti-tumor effect of 153Sm-DTPA-c(CGRRAGGSC) on nude mice model bearing MHCC97-H human liver cancer |
| 投稿时间：2014-06-18 |
| DOI：10.3760/cma.j.issn.0254-5098.2015.02.004 |
| 中文关键词: 肝癌 白细胞介素11类似物 153Sm |
| 英文关键词:Liver cancer Interleukin-11 analogue 153Sm |
| 基金项目:无锡市医院管理中心联合攻关项目(YGZX-1213) |
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| 中文摘要: |
| 目的 探讨153Sm-DTPA-c(CGRRAGGSC)对人MHCC97-H肝癌裸鼠模型移植瘤生长的抑制作用.方法 采用间接法合成153Sm-DTPA-c(CGRRAGGSC)放射性药物.对8种不同细胞系IL-11受体表达,进行Western blot分析,选择肿瘤接种.20只MHCC97-H皮下荷瘤裸鼠按随机数字表法分为4组(对照组,低、中、高剂量组),每组5只.低、中、高剂量组尾静脉分别注入153Sm-DTPA-c(CGRRAGGSC),剂量依序为5.5、11.0和22.0 MBq/0.2 ml,对照组尾静脉注入生理盐水0.2 ml.观察16 d后处死,比较肿瘤的体积,计算抑瘤率;观测标本病理改变;免疫组织化学检测5.5 MBq低剂量组瘤体组织治疗后Ki-67、Bcl-2和IL-11受体表达改变;Western blot检测不同剂量组IL-11受体的变化情况.结果 选择IL-11受体表达最高的MHCC97-H细胞接种.尾静脉内注射153Sm-DTPA-c(CGRRAGGSC)后,早期瘤体中央可出现坏死、干瘪、结痂,后期又出现坏死周围瘤组织继续增长.低、中、高剂量组抑瘤率分别为(22.72±2.76)%、(34.65±2.36)%和(85.13±5.78)%(F＝89.32, P<0.05).免疫组织化学显示,对照组及低剂量组瘤内IL-11受体阳性率分别为(84.13±5.71)%和(61.57±5.98)%(t=13.62, P<0.05),低剂量组瘤细胞排列相对疏松,细胞内染色数量明显减少.低剂量组Ki-67、Bcl-2阳性率均较对照组下降(t=20.91、6.68, P<0.05).Western blot结果显示,随抑瘤作用增加,IL-11受体蛋白表达降低.结论 153Sm-DTPA-c(CGRRAGGSC)能够有效抑制人MHCC97-H肝癌裸鼠模型移植瘤的生长,促进IL-11受体表达下调及诱导凋亡作用. |
| 英文摘要: |
| Objective To observe the antitumor effect of 153Sm-DTPA-c(CGRRAGGSC) on MHCC97-H human liver cancer using a nude mice model.Methods 153Sm-DTPA-c(CGRRAGGSC) was indirectly synthesized by the reaction of 153SmCl3 with DTPA-c(CGRRAGGSC). Western blot was used to detect the expression changes of IL-11 receptor of eight different cell lines. 20 MHCC97-H tumor-bearing nude mice were randomly divided into four groups by random number table method with five mice in each group, administered with different activities of 153Sm-DTPA-c(CGRRAGGSC) by tail vein injection (5.5, 11.0, 22.0 MBq/0.2 ml and physiological saline/0.2 ml in turn). All nude mice were terminated after 16 d then the tumor tissue was observed and analyzed with microscopy, electron microscopy and immunohistochemistry for Ki-67, Bcl-2 and IL-11 receptor. Western blot was used to evaluate the expression changes on IL-11 receptor of tumor tissue at different doses.Results After administration with 153Sm-DTPA-c(CGRRAGGSC), the central region in the early stage of tumor became dry, necrosis, and crusting. In the late stage, tumor continually grew surrounding necrosis tissue. The inhibition rates in the low, middle and higher dose group were (22.72±2.76)%, (34.65±2.36)% and (85.13±5.78)%, respectively(F=89.32,P<0.05). The morphologic results showed that tumor structures were severely damaged along with radiation dose. The results of immunohistochemistry showed that the IL-11 receptor-positive cells in the control group and 5.5 MBq group was (84.13±5.71)% and (61.57±5.98)%(t=13.62,P<0.05), respectively. The Ki-67 and Bcl-2 positive cells were decreased in the injection group (t=20.91,6.68,P<0.05). Western blot analysis showed that the expression of IL-11 receptor protein decreased with antitumor-effect of radiation.Conclusions 153Sm-DTPA-c(CGRRAGGSC) effectively depresses the growth of MHCC97-H human liver cancer and suppresses the expression of IL-11 receptor, and hence could be a promoting agent for the treatment of MHCC97-H human liver cancer. |
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