Effect Of Curcumin Prodrug FM0806-1 On Autitumor In Vitro And In Vivo And The Study In Situ Rat Intestinal Absorption

Introduction: Curcumin, a yellow pigmentin turmeric(Curaumalonga), has been reported to have several phamacological effects including anti tumor, anti inflammat- Ory, anti oxidant, and anti fungi properties. One potential problem with the clinical use of curcumin is its low water insolubility and low bioavailability in vivo. So, in order to enhance the biological activity, we have designed and synthesized a new curcumin prodrug FM0806-1. The present study focused on evaluating the antitumor effect of FM0806-1 in vitro and the inhibitory effects on the animal transplanted tumor, and the mechanism was investigated Preliminary. We also study the absorption in situ rat intestinal of FM0806-1.Objective: To evaluate the antitumor effect of curcumine prodrug FM0806-1 in vitro and in vivo. And to investigate the absorption of FM0806-1 in rats. Methods: (1) The curcumin prodrug FM0806-1 containing serum was prepared by serologic pharmacology method. (2) MTT assay was used to observe the inhibitory effect of FM0806-1 and containing serum on the proliferation of SW1116 cells. (3) A HPLC method was established to analyze the prodrug and its metabolites of containing serum. (4) The morphology change of SW1116 cells was observed with optical microscope. (5) Wright-Giemsa staining was used to study the pathological change of tumor tissue. (6) The expression of proteins related with cell proliferation were detected by Western blot assay. (7) To investigate the anti-tumor effect in vivo, H22 Hepatoma and S180 sarcoma was induced in mice, and CA46 tumor was induced in nude mice. (8) In situ recirculation model was used and the concentration of FM0806-1 were determined by HPLC.Results: (1) FM0806-1 didn't remarkably inhibit the proliferation of SW1116 cells. (2) FM0806-1 containing serum inhibited the proliferation of SW1116 cells in a dose-dependent manner and influenced the morphology of cells. (3) The expressions of Hsp70, Bax protein were enhanced, while Hsp90, Erk1/2, P-Erk1/2 protein were decreased after the treatment of FM0806-1 containing serum. (4) FM0806-1 at dose of 25-100mg/kg showed significant inhibitory effect on H22 and S180 in mice models.There were significantly higher than the same dose of curcumin group. (5) FM0806-1 at dose of 40mg/kg showed significant inhibitory effect on CA46 nude mice xenograft model. (6) Drug has the physical adsorption in four intestinal segments to some extend(pH6.8). In three different pH, drug has different degrees of absorption in four intestina segments.Conclusion: (1) FM0806-1 have no cytotoxicity in vitro. It can release high concentrations of curcumin in vivo, suggesting a bright future as a Cur prodrug. (2) FM0806-1 has significant antitumor activity in vivo, which was higher than cur. But it has the physical adsorption to some extend, so its dosage forms need futher optimization.