IP6 in treatment of liver cancer II. Intra-tumoral injection of IP6 regresses pre-existing human liver cancer xenotransplanted in nude mice

Hepatocellular carcinoma (HCC) is a deadly malignant disease with extremely poor prognosis. Many therapeutic modalities have been proposed, bur consid erable uncertainty still remains about their effectiveness. Inositol hexaph osphate (IP6), a naturally occurring polyphosphorylated carbohydrate, has n ovel anti-cancer function both in vitro and in vivo. We have recently demon strated that IP6 inhibits HepG2 human liver cancel cell line. The aim of th is study was to assess whether IP6 can (a) inhibit tumorigenicity, and (b) suppress or regress the growth of HepG2 cells in a transplanted nude mouse model. To test the inhibition of tumorigenicity, HepG2 cells were treated w ith a Single exposure to 5.0 mM IP6 in vitro; 48 h later they were inoculat ed (1x10(7) cells/mouse) subcutaneously. No tumor was found in mice which h ad received HepG2 cells pretreated with IP6. whereas 71% of mice receiving the same number of control untreated HepG2 cells developed solid tumors at the transplantation site (p<0.03). For a tumor suppression/regression study , when the transplanted tumors reached 8-10 mm in diameter, intra-tumor al injection of IP6 (40 mg/kg) was given for 12 consecutive days, after which the animals were sacrificed. At autopsy, the tumor weight in IP6-treated mi ce was 86% to 1180% (340% aver age) less than that in control mice (0.33 +/ - 0.12 g versus 1.13 +/- 0.25 g, p=0.016). These data show that IP6 inhibit s the formation of liver cancer and regresses pre-existing human hepatic ca ncer xenograft; therefore, it has the potential for clinical use as a preve ntive and therapeutic agent for hepatocellular carcinoma as well.