Enhanced Antitumor Effect of Curcumin Lipsome with Local Hyperthermia in LL/2 Model

Angiogenesis, the growth of new capillary blood vessels, is important for tumor growth and expansion. (Folkman, 1992; Zetter, 1998) Without blood vessels, tumors can not grow beyond a critical size (Bergers and Benjamin, 2003). Thus, tumors must develop their own blood to supply oxygen and nutrients. Anti-angiogenesis therapy can prevent tumor cells from developing a viable blood supply and inhibit the tumor growth. It has been an important therapeutic strategy in the antitumor treatment (Gasparini et al., 2005). Curcumin is small-molecular-weight compound that obtained from the rhizome of the plant Curcuma longa (Goel et al., 2008). Accumulating evidence suggests that curcumin can inhibit carcinogenesis in different organs and the common link between these actions is its antiangiogenic effect (Bhandarkar and Arbiser, 2007). Curcumin may be an ideal anti-angiogenesis drug. First, as a natural antioxidant, curcumin has low toxicity. Phase I and phase II studies have proved that curcumin is well tolerated for cancer patients (Cheng et al., 2001; Dhillon et al., 2008). Second, curcumin is a direct inhibitor of angiogenesis and plays an important role in the down-regulation of proangiogenic proteins, such as VEGF (Arbiser et al., 1998). Third, curcumin can inhibit several signal transduction pathways, including those involving protein kinase C and the transcription factors NF-κB and AP-1. Curcumin’s antiangiogenic effect has been extensively accepted. In order to further enhance curcumin’s antitumor effect, combination other forms therapy would be necessary. Past studies proved that combining antiangiogenic agents with cytotoxic therapies or different antiangiogenic agents has been