多肽PⅢ术中与术后腹腔注射抑制胃癌腹膜转移的研究  

Intraoperative and postoperative intra-peritoneal administration of peptide PⅢ inhibits peritoneal metastasis of gastric cancer

作　　者：白飞虎[1] 杨力[1] 吉清[2] 张燕齐[2] 刘震雄[2] 王治忠[3] 阎丽[2] 王敬博[2] 靳海峰[2] 李婷婷[2] 

机构地区：[1]宁夏医学院附属医院消化内科,银川750004 [2]第四军医大学西京医院全军消化病研究所肿瘤生物学国家重点实验室 [3]第四军医大学预防医学系

出　　处：《中华医学杂志》2006年第46期3260-3263,共4页National Medical Journal of China

基　　金：国家自然科学基金资助项目(30160033)

摘　　要：目的评价多肽PⅢ术中及术后早期腹腔内应用对胃癌腹膜转移的作用。方法48只裸鼠经完整组织块裸鼠胃壁原位种植,建立类似于临床的胃癌腹膜转移模型。每组16只,随机分为①对照组;②术中腹腔多肽灌洗+术后多肽治疗组(关腹前立即用60ml、43℃生理盐水溶解多肽PⅢ200μg冲洗腹腔2次);③术后多肽治疗组。术后1周开始治疗,对照组每只裸鼠与第8、10、12、14、16、18、20、22天腹腔各0·2ml生理盐水腹腔注射;②组和③组与对照组相同的时间分别给予多肽PⅢ2mg/kg腹腔注射,移植后第23天各取6只裸鼠脱颈处死,测定原位肿瘤重量,观察腹膜转移情况。其余裸鼠用于生存率试验。结果对照组、术中腹腔多肽灌洗+术后多肽治疗组和术后多肽治疗组的裸鼠原位肿瘤重量分别为(1·93±0·22)g、(1·81±0·36)g、(1·95±0·45)g,各组间比较,差异无统计学意义;对照组、术后多肽治疗组和术中腹腔多肽灌洗+术后多肽治疗组的裸鼠腹膜转移的瘤结节数分别为(126·3±9·6)个、(64·2±8·3)个、(9·2±1·3)个;其中大于2mm的裸鼠平均腹膜转移结节数分别为(51·2±3·6)个、(21·7±4·9)个、(1·6±0·2)个,与对照组比较,差异均有统计学意义(均P<0·01)。裸鼠生存试验显示术中腹腔多肽灌洗+术后多肽治疗组裸鼠生存时间明显长于对照组及术后多肽治疗组的裸鼠生存时间。结论多肽PⅢ术中及术后腹腔内用药可明显降低裸鼠胃癌腹膜转移的发生,显著延长了裸鼠的生存期,有望成为临床上治疗胃癌腹膜转移的药物。Objective To evaluate the preventive potential of intraoperative or early postoperative local administration of peptide P Ⅲ into the abdominal cavity against peritoneal carcinomatosis. Methods Human gastric cancer cells of the line GC9811 were inoculated subcutaneously into nude mice to cause subcutaneous carcinoma. The 8 th generation cancer was taken out to isolate the cancer cells to be inoculated into the serous membrane at the greater curvature of the stomach. Forty-eight nude BALB/C-nu/nu mice underwent implantation of the 8 th generation cancer cells into the serous membrane at the greater curvature of the stomach via minilaparotomy so as to establish models of peritoneal carcinoma The 48 mice were randomly divided into 3 equal groups ： Group 1 （ control group ） ; Group 2, undergoing intraperitoneal perfusion of 100 p.g of peptide P Ⅲ, and post-operative intraperitoneal perfusion of 2 mg/kg peptide P Ⅲ twice; and Group 3, undergoing post-operative intraperitoneal perfusion of 100 μg/kg peptide Pill twice. Six mice in every group were sacrificed on the day 23 to undergo pathological examination. The other mice in every group were used to evaluate the survival rate. The tumor-bearing mice showing manifestations of failure were killed to undergo pathology. Results The weight of individual tumor was not significantly different among the 3 groups. The number of peritoneal metastatic nodules of Goup2 was （ 9. 2 ±1.3 ）, significantly less than those of Group 1 and 3 [ （ 126. 3 ± 9.6 ） and （64. 2 ± 8. 3 ） respectively, both P 〈 0. 01 ]. The number of metastatic nodules 〉 2 mm of Group 2 was 1.6 ± 0. 2, significantly less then those of Groups 1 and 3 [ （51.2 ± 3.6） and （21.7 ± 4. 9） respectively, both P 〈 0.01 ]. The survival rate of Group 2 was significantly longer than those of Groups 1 and 3 （ both P 〈 0. 01 ）. Conclusion Peptide PⅢ does not significantly inhibit the growth of GC, but significantly reduce the peritoneal metastasis of GC. An ideal targeting che

关 键 词：胃肿瘤 肿瘤移植 肽类 小鼠 裸 腹膜转移 

分 类 号：R735.2[医药卫生—肿瘤]