CDX2 inhibits invasion and migration of gastric cancer cells by phosphatase and tensin homologue deleted from chromosome 10/Akt signaling pathway / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gastric cancer (GC) is one of the most prevalent malignancies in the world today, with a high mortality rate. CDX2 is a Drosophila caudal-related homeobox transcription factor that plays an important role in GC. Phosphatase and tensin homologue deleted from chromosome 10 (PTEN) is an important tumor suppressor which is widely expressed in normal human tissues. The aim of the study was to determine the relationship and mechanism between CDX2 and PTEN in invasion and migration of GC cells.</p><p><b>METHODS</b>pcDNA3-CDX2 plasmids were transfected into MGC-803 cells to up-regulate CDX2 protein, and small interfering RNA-CDX2 was transfected to down-regulate CDX2. The influence of CDX2 or PTEN on cell migration and invasion was measured by invasion, migration and wound healing assays. Western blotting assay and immunofluorescence were used to detect the expression of CDX2, PTEN, phosphorylation of Akt, E-cadherin and N-cadherin. Statistical significance was determined by one-way analysis of variance.</p><p><b>RESULTS</b>The results showed that CDX2 reduced the migration and invasion of GC cells (P < 0.05), and inhibited the activity of Akt through down-regulating PTEN expression (P < 0.05). CDX2 also restrained epithelial-mesenchymal transition of GC cells.</p><p><b>CONCLUSIONS</b>CDX2 inhibited invasion and migration of GC cells by PTEN/Akt signaling pathway, and that may be used for potential therapeutic target.</p>

Lentivirus-mediated RNA interference targeting the ObR gene in human breast cancer MCF-7 cells in a nude mouse xenograft model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>There is a significant association between obesity and breast cancer, which is possibly due to the expression of leptin. Therefore, it is important to clarify the role of leptin/ObR (leptin receptor) signaling during the progression of human breast cancer.</p><p><b>METHODS</b>Nude mice with xenografts of MCF-7 human breast cancer cells were administered recombinant human leptin subcutaneous via injection around the tumor site. Mice in the experimental group were intratumorally injected with ObR-RNAi-lentivirus, while negative control group mice were injected with the same dose of negative-lentivirus. Tumor size was blindly measured every other day, and mRNA and protein expression levels of ObR, estrogen receptor a (ERa), and vascular endothelial growth factor (VEGF) for each group were determined.</p><p><b>RESULTS</b>Knockdown of ObR-treated xenografted nude mice with a high leptin microenvironment was successfully established. Local injection of ObR-RNAi-lentivirus significantly suppressed the established tumor growth in nude mice. ObR level was significantly lower in the experimental group than in the negative control group, while the amounts of ERa and VEGF expression were significantly lower in the leptin group than in the control group (P < 0.01 for all).</p><p><b>CONCLUSIONS</b>Inhibition of leptin/ObR signaling is essential to breast cancer proliferation and possible crosstalk between ObR and ERa, and VEGF, and may lead to novel therapeutic treatments aiming at targeting ObR in breast cancers.</p>

Impact of S100P expression on clinical outcomes of gastric cancer patients with adjuvant chemotherapy of oxaliplatin and its mechanisms / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the impact of the expression of S100P on the prognosis and tumor chemosensitivity in patients with resectable gastric cancer and its mechanisms.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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].</p><p><b>CONCLUSIONS</b>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.</p>