腹腔热灌注化疗对人大肠癌细胞裸鼠腹腔种植的影响

Effects of continuous hyperthermia peritoneal perfusion chemotherapy on peritoneal implantation of human colonic cancer cells in nude mice

目的研究腹腔热灌注化疗(continous hyperthermic peritonealperfusion chemotherapy,CHPPC)的抗癌疗效,探讨 CHPPC 的抗癌机制.方法采用人结肠癌 LoVo 细胞裸鼠腹腔种植模型(n=35),模拟结肠癌术后两个时期,即术后腹腔内散在游离癌细胞期和肉眼可见的广泛癌细胞种植期,进行腹腔灌注(MMC 0.01 g/L～0.02 g/L,10mL/min,41.5℃)治疗,观察其对癌细胞腹腔内种植的影响.结果早期 CHPPC 组的致瘤率为40%(4/10),延期 CHPPC组为60%(6/10),单纯热疗组与单纯化疗组均为80%(4/5),对照组的致瘤率为100%(5/5).生存时间(d):早期 CHPPC 组(59.4±4.9)较单纯化疗组(36.2±8.5)和单纯热疗组(35.6±9.1)明显延长(P=0.000),CHPPC 早期与延期(41.4±7.9)相比差异显著(P=0.001).结论 CHPPC 有明显的抗癌作用,早期 CHPPC 的抗癌作用显著高于延期 CHPPC 及单纯热疗、单纯化疗.实施 CHPPC 的时机是越早越好.

AIM To study the anti-cancer effects and mechanisms of continous hyperthermic peritoneal perfusion chemotherapy (CHPPC). METHODS Male and female BALB/c-nu/nu mice of 4-6 week old were used in the studies and were maintained in a laminar flow cabinet under specific pathogen-free conditions.The animal model of nude mice with peritoneal plant of human colon cancer (LoVo) cell was established. Thirty-five nude mice bearing human colonic cancer cells ( LoVo line) were treated with CHPPC and MMC,which simulate two periods,i.e.,free cancer cell period and visible peritoneal plant period in peritoneal cavity after colorectal cancers resection,and the anti-tumor effect was observed.In the process of CHPPC,the temperature of abdominal cavity was kept at 41.5℃±0.5℃,the duration of perfusion was 30 minutes,and the flow rate was 5 mL/min-10 mL/min. RESULTS The rates of developed peritoneal plants:4/10 mice in early CHPP group,6/10 mice in late CHPPC group,4/5 and 4/5 mice in single chemotherapy and hyperthermia group,and 5/5 mice in the control group. The survival time of early CHPPC group (59.4±4.9 days) was significantly prolonged as compared with late CHPPC group (41.4±7.9 days,P=0.001),single chemotherapy group (36.2±8.5,P=0.000),single hyperthermia group (35.6±9.1,P=0.000) and control group (24.8±8.2, P=0.000).CHPPC can significantly increase the survival time,delay the emerge of ascites,inhibit the tumor growth as against chemotherapy and hyperthermia used alone. CONCLUSION CHPPC has a significant efficacy of preventing developed peritoneal implants of HCC in nude mice.The anti-cancer action of early CHPPC is significantly stronger than that of late CHPPC,single hyperthermothrapy and chemotherapy.