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, but considerable uncertainty still remains about their effectiveness. Inositol hexaphosphate (IP6), a naturally occurring polyphosphorylated carbohydrate, has novel anti-cancer function both in vitro and in vivo. We have recently demonstrated that IP6 inhibits HepG2 human liver cancer cell line. The aim of this 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 with a single exposure to 5.0 mM IP6 in vitro; 48 h later they were inoculated (1 x 10(7) cells/mouse) subcutaneously. No tumor was found in mice which had 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-tumoral 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 mice was 86% to 1180% (340% average) 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 inhibits the formation of liver cancer and regresses pre-existing human hepatic cancer xenograft; therefore, it has the potential for clinical use as a preventive and therapeutic agent for hepatocellular carcinoma as well.
Vucenik
I
I
Department of Medical and Research Technology, University of Maryland School of Medicine, Baltimore 21201, USA.
Zhang
Z S
ZS
Shamsuddin
A M
AM
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010833:Phytic Acid / Q000627:therapeutic use*; D013997:Time Factors; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D010833:Phytic Acid