卡培他滨抑制裸鼠肝癌切除术后复发转移的作用

Capecitabine in inhibition of recurrence and metastasis after liver cancer resection in nude mice

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 D2 0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 2 4只LCI D2 0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 [(16 8± 2 0 6 )mm3 ]以及AFP水平 [(10 7± 90 )ng/ml]明显小于对照组肝癌体积 [(316 2± 6 90 )mm3 ]以及AFP水平 [(15 19± 80 7)ng/ml],P <0 0 5 ;裸鼠肝内复发率和肺转移率也明显下降 ,P <0 0 5。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 0 5 )。 结论 CAP治疗能抑制高转移性人肝癌切除术后的复发转移。

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×b2×05. 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<005). 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.