Chinese Journal of Lung Cancer (Apr 2008)
Effects of combined therapy of Phosphatidylinositol 3p-Kinase and Paclitaxel in human lung cancer nude mice model
Abstract
Background and objective Increasing evidence suggests that aberrant activation of PI3K/Akt is involved in many human cancers, and that inhibition of the PI3K/Akt pathway might be a promising strategy for cancer therapy. The aims of this study is to evaluate the effects of combined therapy of Phosphatidylinositol 3-Kinase inhibitor(LY294002 ) and Paclitaxel in athymic mice xenogeneic transplant model of lung cancer and to reveal the possible mechanisms involved．Methods Eighteen athymic mice were randomly divided into 3 groups (control, paclitaxel alone and paclitaxel plus LY294002), and were treated respectively. Athymic mice xenogeneic transplant model was establishedby inoculation (sc) with A549 lung cancer cells. Body mass (BM) and diameter of tumor mass were measured. Furthermore,the protein expressions of CyclinD1，bcl-2 and bax in tumor tissues were analyzed with immunohistochemistry. Results The tumor-inhibiting rate of paclitaxel plus LY294002 (92.47%) was significantly higher than the paclitaxel alone (65.59%)（P<0.05).The protein expression of bcl-2 in paclitaxel plus LY294002 group were significantly higher, while bax wassignificantly lower than that in the other two groups (P <0.05). The protein expression of CyclinD1 was significantly lower than the control group (P <0.05). Conclusion LY294002 can enhance the effects of paclitaxel in the treatment of lung cancer and CyclinD1, bcl-2 and bax may be involved in its inhibitory effects.
