Zhou Jian, Tang Zhao-You, Fan Jia, Wu Zhi-Quan, Ji Yuan, Xiao Yong-Sheng, Shi Ying-Hong, Li Xiao-Ming, Sun Qi-Man, Liu Yin-Kun, Ye Sheng-Long
Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China.
Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):6030-7.
This study was to investigate the effect of capecitabine on recurrent tumor and metastasis after curative resection of liver cancer, xenograft of a highly metastatic human hepatocellular carcinoma (HCC) tumor (LCI-D20), with special reference to the expression of platelet-derived endothelial cell growth factor (PD-ECGF).
LCI-D20 and LCI-D35 (a low metastatic human HCC model) liver tumors were orthotopically implanted in 96 nude mice and divided into a treatment group (24 LCI-D20 mice and 24 LCI-D35 mice) and a prevention group (48 LCI-D20 mice). In the prevention group, curative resection of liver tumors was done 10 days after the orthotopic implantation of LCI-D20 tumor. Arabic gum (control), 5-fluorouracil (5-FU), and capecitabine were administrated respectively to all of the 96 mice.
In the treatment group, tumor volume was 468 +/- 138, 442 +/- 81, and 240 +/- 119 mm3 (P<0.01) in the control, 5-FU, and capecitabine subgroups, respectively, in LCI-D20 mice, whereas it was 168 +/- 35, 164 +/- 23, and 144 +/- 21 mm3 (P>0.05), respectively, in LCI-D35 mice. In the prevention group, incidence of liver recurrence in the control, 5-FU, and capecitabine subgroups was 100, 100, and 50%; lung metastasis being 100, 100, and 17%; and life span being 31 +/- 5, 37 +/- 5, and 77 +/- 19 days, respectively. PD-ECGF was highly expressed in HCC and its metastatic tissues in LCI-D20 mice and hardly expressed in HCC tissues in LCI-D35 mice.
Capecitabine inhibits tumor growth and metastatic recurrence after resection of HCC in highly metastatic nude mice model. The effect of capecitabine may be attributed to the high expression of PD-ECGF in tumors.
本研究旨在探讨卡培他滨对肝癌根治性切除术后肿瘤复发及转移的影响,以高转移性人肝细胞癌(HCC)肿瘤(LCI-D20)异种移植瘤为研究对象,并特别关注血小板衍生内皮细胞生长因子(PD-ECGF)的表达。
将LCI-D20和LCI-D35(低转移性人HCC模型)肝肿瘤原位植入96只裸鼠体内,并分为治疗组(24只LCI-D20小鼠和24只LCI-D35小鼠)和预防组(48只LCI-D20小鼠)。在预防组中,LCI-D20肿瘤原位植入10天后进行肝肿瘤根治性切除。分别对96只小鼠给予阿拉伯胶(对照组)、5-氟尿嘧啶(5-FU)和卡培他滨。
在治疗组中,LCI-D20小鼠的对照组、5-FU组和卡培他滨组的肿瘤体积分别为468±138、442±81和240±119mm³(P<0.01),而在LCI-D35小鼠中,其肿瘤体积分别为168±35、164±23和144±21mm³(P>0.05)。在预防组中,对照组、5-FU组和卡培他滨组的肝复发率分别为100%、100%和50%;肺转移率分别为100%、100%和17%;生存期分别为31±5、37±5和77±19天。PD-ECGF在LCI-D20小鼠的HCC及其转移组织中高表达,而在LCI-D35小鼠的HCC组织中几乎不表达。
在高转移性裸鼠模型中,卡培他滨可抑制HCC切除术后的肿瘤生长及转移复发。卡培他滨的作用可能归因于肿瘤中PD-ECGF的高表达。