临床肿瘤学杂志

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重组人血管内皮抑素间插联合顺铂对H22小鼠腹水瘤抑制作用的研究

魏红梅1,秦叔逵2,殷晓进3,陈亚利3,华海清2,王 琳2,杨宁蓉2,陈映霞2,刘秀峰2

  

  1. 1 266042 山东青岛 青岛市中心医院肿瘤综合治疗科2 210002 解放军八一医院全军肿瘤中心肿瘤内科3 210042江苏先声药物有限公司研究院
  • 收稿日期:2013-09-13 修回日期:2013-11-02 出版日期:2014-02-28 发布日期:2014-02-28
  • 通讯作者: 秦叔逵

Research on intercalated combination of recombinant human endostatin and cisplatin in H22 tumor ascite model

WEI Hongmei, QIN Shukui, YIN Xiaojin, CHEN Yali, HUA Haiqing, WANG Lin, YANG Ningrong, CHEN Yingxia, LIU Xiufeng.

  

  1. Deparment of Oncology, Qingdao Central Hospital, Qingdao 266042, China
  • Received:2013-09-13 Revised:2013-11-02 Online:2014-02-28 Published:2014-02-28
  • Contact: QIN Shukui

摘要:

目的 观察重组人血管内皮抑制素(恩度)间插联合顺铂腹腔内注射治疗小鼠腹水瘤的疗效和安全性。方法 采用肝细胞癌H22腹水瘤细胞株建立小鼠腹水瘤模型。120只造模后的ICR小鼠随机分为4组:对照组(生理盐水d1~d10)、恩度组(恩度8mg/kg,d1~d5,d7~d10,生理盐水d6)、顺铂组(顺铂004mg/kg,d6,生理盐水d1~d5,d7~d10)及恩度联合顺铂组(恩度8mg/kg,d1~d5,d7~d10;顺铂0.04mg/kg,d6),每组30只,每只小鼠腹腔注射的药物体积均为0.2ml。记录各组小鼠腹水体积、腹水中肿瘤细胞、红细胞计数以及生存期;观察各组荷瘤小鼠腹膜和腹腔脏器种植转移情况;检测各组小鼠的腹膜渗透性、血常规和肝肾功能;流式细胞仪检测各组小鼠腹腔积液中肿瘤细胞凋亡情况。结果 与对照组相比,恩度组和顺铂组和恩度联合顺铂组均能减少荷瘤小鼠腹腔积液的体积、肿瘤细胞数和红细胞数,延长荷瘤小鼠的生存时间。在上述指标中,恩度联合顺铂组与恩度组和顺铂组比较,差异有统计学意义(P<0.05)。恩度联合顺铂组小鼠腹腔积液中肿瘤细胞的凋亡率显著高于恩度组和对照组(P<0.05),但与顺铂组比较差异无统计学意义(P>0.05);恩度联合顺铂组小鼠的腹膜渗透性明显低于顺铂组和对照组(P<0.05),但恩度联合顺铂组与恩度组比较差异无统计学意义(P>0.05)。恩度联合顺铂组小鼠的体重增加及腹腔种植转移均少于其他3组。各组小鼠均未出现血常规和肝肾功能明显异常。结论 恩度间插联合顺铂腹腔内应用治疗小鼠H22腹水瘤疗效显著,安全性好。

Abstract:

Objective To observe the effects and safety of intercalated combination of recombinant human endostatin(endostar) and cisplatin by intraperitoneal injection in mice model bearing tumor ascite. Methods The tumor ascites model were established with hepatocellular carcinoma H22 cell lines by intraperitoneal injection. One hundred and twenty ICR mice were randomly assigned into 4 groups: control group(normal saline d1-d10), endostar group(endostar 8mg/kg,d1-d5, d7-d10; normal saline d6), cisplatin group(cisplatin 0.04mg/kg,d6; normal saline d1-d5, d7-d10) and combined group(endostar 8mg/kg, d1-d5, d7-d10;cisplatin 0.04mg/kg,d6). Body weight, volume of ascites, the number of tumor cells and red cells were measured. The peritoneum permeability assay, blood routine, liver function and renal function were tested in each group respectively. Implantation metastasis of tumor was observed in abdominal cavity of mice. Apoptosis of tumor cells in the ascites fluid were detected by flow cytometry. Survival time of each mouse was recorded. Results Compared with the control group, endostar group, cisplatin group and combined group could inhibit ascites accumulation, reduce the counts of tumor cells and red cells in the ascites fluid and tumor burden of abdominal cavity, as well as prolonging survival of mice(P<0.05). In those above items, combined group showed statistic significance compared with endostar group and cisplatin group(P<0.05). Combined group significantly increased apoptosis of tumor cells compared with control group and endostar group(P<0.05), but showed no difference with cisplatin group(P>0.05). Combined group obviously inhibited the peritoneum permeability compared with control group and cisplatin group(P<0.05), but showed no difference with endostar group(P>0.05). Peritoneal metastasis and weight gain were less in combined group compared with the other 3 groups. Blood routine, liver function and renal function of the each group were normal. Conclusion The intercalated combination of endostar and cisplatin by intraperitoneal injection treating H22 mice bearing tumor ascite has ideal effect and safety.

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