卡培他滨抑制裸鼠肝癌切除术后复发转移的作用

摘要

Objective　To evaluate the inhibition effect of capecitabine ［a new prodrug of 5-fluorouracil which is dependent on platelet-derived endothelial cell growth factor (PD-ECGF)］, on recurrence and metastasis after liver cancer resection in LCI-D20, a nude mice model with highly metastatic human liver cancer.　Methods　The protein level of PD-ECGF was determined by using immunohistochemical method in 18 liver cancer samples and 18 lung metastasis samples of LCI-D20. The liver tumors were radically removed in 24 LCI-D20 nude mice on day 10 after their orthotopic implanting. Capecitabine, 5-fluorouracil, and arabic gum (control) via oral administration were used on day 3 after their removal. All treatment lasted 3 weeks. The tumor size was calculated by using the formula: V=a×b2×0.5. The AFP levels in the plasma of the nude mice were detected by radioimmunoassay. Lung metastasis was evaluated by HE staining in lung samples.　Results　PD-ECGFs were expressed in all 18 liver cancer and 18 lung metastasis samples. After the intervention of capecitabine, the size of recurrent intrahepatic tumor ［(168±206）mm3］ was smaller than that of the control ［(3 162±690）mm3］. The AFP level ［(107±90）ng/ml］ was also significantly lower than that of the control ［(1 519±807）ng/ml］ (P＜0.05). The rate of intrahepatic recurrence and lung metastasis decreased significantly (P＜0.05). However, no difference was noted in the above characteristics between the 5-fluorouracil group and the control group.　Conclusion　Capecitabine may inhibit the recurrence and metastasis of highly metastatic liver cancer after its resection.%目的探讨血小板衍化内皮细胞生长因子（PD-ECGF）依赖的化疗药卡培他滨（Capecitabine，CAP）对肝癌切除术后复发转移的作用。方法用免疫组化方法检测18例LCI-D20裸鼠人肝癌高转移模型中肝癌和肺转移灶中的PD-ECGF表达。用24只LCI-D20裸鼠，于肝癌组织原位种植后第10天行根治性肝癌切除术，术后第3天分别采用CAP和5-氟尿嘧啶治疗。停药后第3天处死裸鼠，观察肝内有无肿瘤复发。若有则测量复发灶的长短径。检测裸鼠肝功能和血浆甲胎蛋白（AFP）水平，并用HE染色检测肺转移。结果 18例肝癌和肺转移灶组织中均表达PD-ECGF。CAP治疗后，肝内复发癌灶体积［（168±206）mm3］以及AFP水平［（107±90）ng/ml］明显小于对照组肝癌体积［（3 162±690）mm3］以及AFP水平［（1 519±807） ng/ml］，P＜0.05；裸鼠肝内复发率和肺转移率也明显下降，P＜0.05。而5-氟尿嘧啶治疗组与对照组比较以上指标差异均无显著性意义(P＞0.05)。结论 CAP治疗能抑制高转移性人肝癌切除术后的复发转移。