ABSTRACT
Background: The family of curcumin has biological functions, such as anti-oxidative and anti-inflammatory action. Recently, its inhibitory effect on angiogenesis in tumor has been suggested. However, it is not clear how curcumin (CUR) or its derivatives have such in vivo effects. Objective: To quantitatively examine the in vivo effects of CUR or its reduced derivative, tetrahydrocurcumin (THC), on neocapillarization in nude mouse tumors induced by hepatocellular carcinoma (HepG2) cells. Methods: In male BALB/c nude mice (20-25g b.w.), a dorsal skin-fold chamber was implanted, and 30 ml of 2 x 10⁶ human HepG2 cells were inoculated onto the upper layer. The mice were divided into 4 groups: control (CON) supplemented with 0.1% DMSO, HepG2-implanted mice supplemented with DMSO, CUR or THC groups supplemented with CUR or THC (3,000 mg/kg bw), respectively. On the day of the experiment, days 7 and 14, the microcirculation within the chamber was observed using fluorescence videomicroscopy. Based on the recorded video images, capillary vascularity (CV) was measured on the tumor surface. Results: The CV increased in tumors on days 7 and 14 in the HepG2-implanted mice. In the CUR and THC groups, the CV levels were lower than the control level. Furthermore, on day 14, the CV level of THC group was lower than the CV level of the age-matched group. This indicates that HepG2-induced neocapilllaries were reduced markedly by supplementation of THC. Conclusion: THC is potent for suppression of neocapillarization involved in tumor progression.
ABSTRACT
Background: In a tumor, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial cell growth factor (VEGF) are induced to promote angiogenesis for the growth and metastasis of cells. There have been very few studies to examine in vivo relation between HIF-1α and VEGF during tumor progression. Objective: To study the relationship between HIF-1α and VEGF expressions under neovascularization induced by hepatocellular carcinoma cells (HepG2) implanted in nude mice. Methods: Male BALB/c-nude mice 8-10 weeks of age were used. A chamber was prepared on the dorsal skin in which HepG2 was transplanted to induce a tumor. On the day of the experiment, and on days 2, 7, and 14, microcirculation within the chamber was observed using fluorescence videomicroscopy. Based on the recorded video images, capillary vascularity (CV) was measured to examine tumor neovascularization. VEGF expression was measured in blood (serum) withdrawn, using enzyme immunoassay, while HIF-1α expression was measured on samples isolated from tumor tissue, using immunohistochemistry. Results: The measured CV significantly increased on day 7 and 14 compared to the aged-matched controls (p \< 0.05). HIF-1α markedly expressed on day 2, and the expression declined on day 7 and 14 post-inoculation. VEGF expression in serum increased more on day 7 and 14 than on day 2. HIF-1α expression decreased with the increase in VEGF expression from 2 to 14 days after HepG2 implantation, showing a reverse correlation. Conclusion: HIF-1α expression existed prior to both VEGF expression and neovascularization in the tumor. An inhibitor of HIF-1α might be a therapeutic agent for reducing neovascularization via adaptation to hypoxia in tumors.