We recently found that down-regulation of HDGF inhibits anchorage-independent growth and in vitro invasion in non-small cell lung cancer cells A549, H226, H358 and H1944. To determine the role of HDGF in in vivo tumor growth, we performed two types animal experiments using subcutaneous nude mouse models. First, A549 cells either transfected with siRNA-HDGF, scramble siRNA, or lipofectamine alone were inoculated subcutaneously into nude mice (5 mice each group). Tumor sizes were measured every 2 days. After 3 weeks, mice were sacrificed due to the large tumor burden in the control mice. We observed a significantly slower tumor growth in mice inoculated with siRNA-HDGF treated cells compared with mice inoculated with cells treated with scramble siRNA or lipofectamine alone (P = 0.03, P = 0.018, respectively). We then investigated whether siRNA-HDGF has a therapeutic potential for treating lung cancer. We inoculated A549 cells subcutaneously into nude mice and allowed tumors to form at about 100 mm3 in volume. Mice were randomized (5 mice each group) and were treated with either siRNA-HDGF (conjugated with polyethylenimine, PEI), scramble siRNA (with PEI), or PEI alone once every 3 days intra-peritonea (IP) for 5 times. A significant inhibition of tumor growth was observed between the siRNA-HDGF group and the PEI alone group (P = 0.033). No difference was found between the scramble siRNA group and the PEI alone group (P = 0.875). The animals treated with siRNAs did not show any sign of toxicity during the experimentation. Our data suggest that HDGF is important in lung cancer progression and may be a novel therapeutic target. (Supported by Department of Defense grants DAMD17-01-1-01689-1 and W81XWH-04-1-0142)

[Proc Amer Assoc Cancer Res, Volume 47, 2006]