| The antitumor activities combinated gefitinib targeted EGFR with the traditional chemotherapeutic drug paclitaxel were evaluateed by MTT assay. Gefitinib(Iressa) is a compound of anilinoquinazoline structure derivatives with HER1 tyrosine kinase inhibitory activity, while Paclitaxel (Taxol) is a kind of mitotic inhobitor. The two drugs act in different ways based on separated mechanism against tumor cells. Gastric cancer (also called stomach cancer) is now a kind of cancer of high morbidity and mortality in China. Up to now, rarely any targeting therapies or combined targeting drug with traditional chemotherapeutic drug therapies are applied for the treatment of gastric cancer. In fact, HER1 is over-expressed in 33%～74% gastric cancers. In this study, we used Gefitinib which is targeting HER1 and paclitaxel which is a traditional chemotherapeutic drug in combination and observed their combinational efficacy, interactions (synergism or addition) and the possible mechanism of the synergistic interactions. Different proportion of the two drugs was used against gastric cancer cells with HERs over-expression to determine their interactions (synergism or addition). When the concentration proporation of the two drugs was in 330:1 and the overall inhibitory ratio was 60～80%, the interaction of the two drugs showed favorable synergism as determined by combination index (CI) analysis. Western Blot analysis was used to find the expression of HERs, phosphorylated HERs and signaling molecules in the downstream signaling pathway related to HERs, such as Akt/phosphorylated Akt. Apoptosis was potentiated by the co-admimistration compared with the single treatment of the respective drug which was confirmed by analyses of Hochest33342 staining and the expressions of apoptosis-related proteins. The results suggest that the combination of the two drugs in proper ratio could inhibit the proliferation of HERs over-expressed gastric cancer cells synergistically. |
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