PT  - JOURNAL ARTICLE
AU  - Wang, Rui
AU  - Fan, Qingxia
AU  - Hu, Xiangjie
AU  - Wang, Liuxing
AU  - Zhao, Peirong
AU  - Wang, Ruilin
TI  - Insulin-Enhanced Antitumor Effect of 5-Fluorouracil <em>in vivo</em>
AID  - 10.1007/s11805-008-0277-y
DP  - 2008 Aug 01
TA  - Chinese Journal of Clinical Oncology
PG  - 277--280
VI  - 5
IP  - 4
4099  - http://www.cancerbiomed.org/content/5/4/277.short
4100  - http://www.cancerbiomed.org/content/5/4/277.full
SO  - Cancer Biol Med2008 Aug 01; 5
AB  - OBJECTIVE To determine if insulin treatment can enhance the antitumor effect of 5-fluorouracil (5-FU), and to explore the mechanism of the enhancement of insulin.METHODS S180 sarcoma, H22 liver cancer and human Eca-109 esophageal cancer cells were transplanted into nude mice to evaluate the inhibitory effect on tumor growth of insulin alone or in combination with 5-FU. The levels of serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) were determined.RESULTS Compared with 5-FU treatment alone, the tumor weight of H22 liver cancer and S180 sarcoma was reduced further with high, medium and low-dose insulin (0.09, 0.06, 0.03 U/20 g) + 5-FU treatment. When a high dosage of insulin + 5-FU was administered, tumor weight was significantly reduced (P < 0.05). The inhibitory rate of growth of S180 sarcoma and H22 liver cancer reached 50.2% and 51.4%, respectively, which was significantly higher than 24.9% and 27.9% in the group receiving 5-FU alone (P < 0.05). High, medium and low-dose insulin combined with 5-FU significantly inhibited the growth of Eca-109 cancer cells (P < 0.05). Compared with the control group, the level of serum IGF-1 decreased (P < 0.05), whereas the level of serum IGFBP-3 slightly increased in the 5-FU ± insulin groups (P > 0.05). In mice with H22 liver cancer and S180 sarcoma the IGF-1 level with high-dose insulin + 5-FU treatment was significantly lower compared to treatment with 5-FU alone (P < 0.05), but the difference was not significant in mice transplanted with esophageal cancer cells.CONCLUSION Insulin can enhance the anti-tumor effect of 5-FU without significantly increasing 5-FU toxicity. Although changes in the serum IGF-1 or IGFBP-3 level do not explain the mechanism of the insulin-induced enhancement on 5-FU on growth, a decrease in the level of serum IGF-1 and an increase in serum IGFBP-3 may be important in the chemotherapeutic response.