Capecitabine inhibits postoperative recurrence and metastasis after liver cancer resection in nude mice with relation to the expression of platelet-derived endothelial cell growth factor

Clin Cancer Res. 2003 Dec 1;9(16 Pt 1):6030-7.

Abstract

Purpose: 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).

Experimental design: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Capecitabine
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / prevention & control
  • Carcinoma, Hepatocellular / surgery*
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / therapeutic use*
  • Fluorouracil / analogs & derivatives
  • Humans
  • Liver Neoplasms, Experimental / metabolism
  • Liver Neoplasms, Experimental / prevention & control
  • Liver Neoplasms, Experimental / surgery*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Recurrence, Local / drug therapy*
  • Postoperative Care
  • Thymidine Phosphorylase / metabolism*
  • Transplantation, Heterologous

Substances

  • Antimetabolites, Antineoplastic
  • Deoxycytidine
  • Capecitabine
  • Thymidine Phosphorylase
  • Fluorouracil