多肽P Ⅲ术中与术后腹腔注射抑制胃癌腹膜转移的研究

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60 ml、43℃生理盐水溶解多肽PⅢ 200 μg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0.2 ml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PⅢ 2 mg/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2 mm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.

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

OBJECTIVE: To evaluate the preventive potential of intraoperative or early postoperative local administration of peptide PIII 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 8th 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 8th 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 microg of peptide PIII, and post-operative intraperitoneal perfusion of 2 mg/kg peptide PIII twice; and Group 3, undergoing post-operative intraperitoneal perfusion of 100 microg/kg peptide PIII 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 Group 2 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 chemotherapy, intra-operative application of peptide PIII into the abdominal cavity plus intraperitoneal perfusion is an attractive and promising strategy to prevent peritoneal metastasis of GC.