术前植入5-Fu缓释剂对大肠癌的治疗

Preoperative implant of 5-fluorouracil sustained release in the patients with colorectal cancer

目的探讨大肠癌术前直肠黏膜植入5-Fu缓释剂(5-FuSR)后,药代动力学、毒副作用、肿瘤细胞凋亡和增殖及其调控基因的变化。方法将25例大肠癌随机分为两组:试验组(Ⅰ组)和对照组(Ⅱ组),两组均在手术前后取癌组织及癌旁组织,观察癌组织病理形态和识别凋亡癌细胞,SP免疫组化法检查给药前、手术后肿瘤细胞增殖细胞核抗原(PCNA)、凋亡、p53及Bcl-2基因表达状况。结果Ⅰ组用药后24、48、72h外周5-Fu血药浓度维持较稳定,差异无显著性(P>0·05);72h时门静脉血浓度显著大于外周血(P=0·013);癌组织浓度显著高于癌旁组织。Ⅰ组术后凋亡指数显著高于术前(P<0·001);术后癌细胞的增殖指数较术前明显降低(P<0·01);凋亡抑制基因Bcl-2表达术后较术前显著下调(P=0·03);p53基因突变与非突变者,二者术后Bcl-2表达均较术前下调。结论直肠黏膜下植入抗肿瘤药是术前区域性化疗的最佳途径;5-FuSR药代动力学和药效学满意,大肠癌细胞凋亡增加,凋亡抑制基因Bcl-2表达明显下调,并且对p53基因突变者亦有较好疗效。

Objective To study the pharmacokinetic changes, harmful effect, apoptosis, proliferation and control gene changes after implantation of 5-Fluorouracil Sustained Release （5-Fu SR） into the rectal submucosa of patients with colorectal cancer. Methods 25 patients with colorectal cancer were randomly divided into two groups. Immunohistochemistry （SP） was performed to detect the expression of PCNA, p53 and bcl-2 gene. Results In the stud- y group, the difference in serum concentrations of 5-Fu in peripheral veins at 24, 48 and 72 hours was not signifi- cant （P 〉 0. 05 ）. At 72 h, the drug concentration was higher in mesentery venous blood than in peripheral blood （P = 0. 013 ）, and was higher in tumor tissue than in adjacent tissue （P = 0. 010）. Post-operation AI was higher than that before operation（P 〈0. 01 ）, and PI was lower post-operation vs. pre-operation（P 〈0. 01 ）. The proportion of apoptosis increased, and the expression of bcl-2 decreased. The expression of bcl-2 in patients with and without p53 mutation decreased post-operation. Conclusion Implanting 5-FuSR into rectal mucosa is the best way for adjuvant chemotherapy against colorectal cancer. It presents a significant pharmacokinetics and pharmacodynamic effect. In addition, it inhibits bcl-2 expression while induces apoptosis of tumor cells.