Expression of taxol resistance gene 1 correlates with gastric cancer patient clinical outcome and induces taxol resistance.

In the present study, we investigated the effect of the taxol resistance gene 1 (TXR1) on taxol resistance in gastric cancer (GC). Immunohistochemistry was performed in order to assess the expression pattern of TXR1 in paraffin-embedded specimens of 107 GC patients who underwent radical D2 gastrectomy with long-term follow-up. In order to determine whether TXR1 expression plays a role in taxol resistance in GC cells, TXR1 was exogenously expressed or knocked down by siRNA in the absence and presence of taxol treatment, and cell proliferation was determined using the MTT assay. TXR1, thrombospondin-1, multidrug resistance protein mRNA and protein expression levels and certain drug resistance-related genes were determined by real time-PCR. There was a significant correlation between TXR1 expression and distant metastasis. Patients whose tissue biopsies tested negative for TXR1 expression had a higher post-operative 5-year survival rate than patients who had TXR1-positive tissue biopsies, even in the advanced cancer group. Exogenous expression of TXR1 in BGC823 cells induced taxol resistance, and siRNA knockdown of TXR1 sensitized human GC cells to taxol. The results show that low expression of TXR1 is correlated with a favorable prognosis in GC patients and that TXR1 likely plays a role in taxol resistance in GC cells.