Inhibitory effect of the low-toxic exogenous aryl hydrocarbon receptor modulator 3'3-diindolylmethane on gastric cancer in mice.

Abstract

3'3-Diindolylmethane (DIM) has been proved to exhibit anticancer properties in many solid tumors. In our previous study, we demonstrated that DIM inhibited SGC7901 cell proliferation by inducing apoptosis and delaying cell cycle progression. Herein, we further explored the anti-tumor effect of DIM on SGC-7901 tumor bearing mice. Tumors were excised, weighed, and tested by western blot and TdT-UTP nick-end labeling (TUNEL) assay. Blood samples were collected for biochemical analysis. The expression levels of AhR and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) protein were evaluated by western-blot assay. Our data show that with the increase of DIM dose (0, 5, 10, 20 mg/kg/day), AhR protein gradually decreased as CYP1A1 protein increased. The weight of the tumors found in the treated animals was significantly lower than that of the control group (0.845±0.096 vs. 1.275±0.236 g, 0.768±0.161 vs. 1.275±0.236 g, 0.607±0.106 vs. 1.275±0.236 g, P<0.05). TUNEL test showed that DIM induced increased apoptosis in the treatment groups in a dose-dependent manner. Blood tests also indicated that DIM showed no toxic effect on animal weight or liver and kidney function. These results indicated that DIM agent could be a safe and potent drug in therapy of gastric cancer.