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ABSTRACT: 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.
Molecular Medicine Reports 11/2010; 3(6):1071-8. DOI:10.3892/mmr.2010.371 · 1.55 Impact Factor
Chinese medical journal 11/2010; 123(22):3364-6. DOI:10.3760/cma.j.issn.0366-6999.2010.22.038 · 1.05 Impact Factor
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ABSTRACT: To investigate the impact of the expression of S100P on the prognosis and tumor chemosensitivity in patients with resectable gastric cancer and its mechanisms.
The expression of S100P was analyzed in 121 resected primary gastric cancer tissues by using tissue array of immunohistochemistry excised from January 2003 to December 2007. The patients received adjuvant chemotherapy with oxaliplatin. The pEGFP-S100P plasmid was constructed and was transfected into BGC823 cell line to establish gastric cancer cell line with over-expression of human S100P, BGC823-S100P. The expression level of S100P was determined by real-time PCR and Western blot assay. The chemosensitivity of BGC823-S100P cell line to oxaliplatin was detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay.
The S100P was positively expressed in 64 tumors (52.9%, 64/121). Although there was no significant relation between the expression of S100P and tumor T staging (P = 0.683), N staging (P = 0.472), M staging (P = 0.770) and differentiation (P = 0.553), Wilcoxon test showed that the 5-year cumulative survival rate of patients with positive S100P expression was significantly higher than that of patients with negative expression (20.3% vs. 3.5%, P = 0.034). Furthermore, overexpressed of S100P was found in the BGC823 cell line, BGC823-S100P. The mRNA and protein level of S100P in pEGFP transfected BGC823-S100P cell lines were significantly higher than those in control group (8.42 ± 1.38 vs. 0.83 ± 0.11 and 3.52 ± 0.48 vs. 0.97 ± 0.19, all P < 0.05). It indicated with MTT assay that the half-inhibitory concentration (IC(50)) to oxaliplatin decreased in BGC823-S100P cells, and was significantly lower than that in vector-only transfected cells [(142 ± 16) mg/L vs. (266 ± 11) mg/L, P = 0.032].
S100P may also be a potentially novel independent prognostic factor in gastric cancer patients following curative resection. And it could improve the cumulative survival of the patients through enhancing the chemosensitivity of tumor cell line to oxaliplatin.
Zhonghua wai ke za zhi [Chinese journal of surgery] 07/2010; 48(13):1004-8.
Chinese medical journal 01/2009; 121(23):2463-4. · 1.05 Impact Factor