The effect of 5-fluorouracil (5-FU) chemotherapy for gastric cancer (GC) is limited by drug-resistance. To conquer this drug-resistance, various treatments including combination therapy have been used, but the overall survival has not been improved yet. In our current study, 5-FU resistant GC cells, SGC7901/FU and MGC803/FU, were established by long term exposure to 5-FU, and the proliferation capability of these resistant cells was verified to be reduced. The drug related proteins, MDR1 and P-gp were up-regulated in resistant cells compared to the parental cells. We further found proliferation and tumor growth suppressed effects of epigallocatechin gallate (EGCG), which is the predominant polyphenolic catechin constituent in green tea, on both the 5-FU resistant cells and the SGC7901/FU xenograft. Furthermore, an interesting results showed that reversal of 5-FU resistance of GC cells by EGCG treatment in vivo and in vitro. In the molecular study, We also found that EGCG suppressed the expression of both MDR-1 and P-gp at mRNA and protein levels in vivo and in vitro. Western blot and ELISA assay revealed that EGCG was able to inhibit VEGF secretion and expression, and its up-stream signal regulator, transcription factor activator protein 2A (TFAP2A) was also down-regulated by EGCG, our results indicated that TFAP2A/VEGF axis is one of the critical pathway inhibited by EGCG for cell proliferation and 5-FU resistance. Taken together, our data suggested that EGCG inhibits GC growth and reverses 5-FU resistance of GC through inactivation of TFAP2A/VEGF pathway and down-regulation of MDR-1 and P-gp expression.

The FOXO6 correlated with tumor progression in a wide range of carcinomas, yet little is known in gastric cancer. The expression of FOXO6 and matrix metallopeptidase 9 (MMP-9) was assessed by immunohistochemistry in 192 gastric carcinoma specimens. The correlation between FOXO6 expression with MMP-9, clinicopathological/prognostic value in gastric cancer was examined. FOXO6 overexpression was significantly associated with depth of invasion, lymph node metastasis and stage of disease. In univariate and multivariate analyses, FOXO6 was an independent prognostic factor for both overall survival (OS) and recurrence-free survival (RFS). Moreover, FOXO6 over-expression was correlated with poor prognosis in patients subgroups stratified by tumor size, depth of invasion and lymph node metastasis. FOXO6 expression was increased in both prominent serosal invasion group and lymph node metastasis group. In addition, FOXO6 expression was positively correlated with MMP-9 among 192 gastric cancer tissues. Patients with FOXO6 over-expression had poor OS and shorter RFS in low and high invasiveness groups. Furthermore, stratified analysis showed that the TNM stage I patients with high FOXO6 expression had poor prognosis than those with low FOXO6 expression. In conclusion, FOXO6 overexpression promotes tumor aggressiveness and prognosis, and could be a promising target for prognostic prediction in gastric cancer patients.Condensed abstractThe aim of this study was to analyze the role of FOXO6 in patients with gastric carcinoma. FOXO6 may play an important role on tumor invasion, metastasis and prognosis. It may also serve as a novel target for prognostic prediction.

In view of the acceptable morbidity and mortality rates we propose that CRS combined with HIPEC presents an effective and safe treatment modality for patients with gastric cancer, especially in cases where optimal cytoreduction is achieved before the HIPEC procedure.

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Bioinspired artificial nanochannels for molecular and ionic transport have extensive applications. However, it is still a huge challenge to achieve an intelligent transport system with high selectivity/efficiency and controllability. Inspired by glutathione transport across the plasma membrane via redox regulation, we herein designed and fabricated a redox-reactive artificial nanochannel based on the host–guest chemical strategy. The nanochannel platform achieved high selectivity/efficiency for the identification and transmission of glutathione in the confined space. In addition, this nanochannel can switch between the ON and OFF states through the redox reaction. This redox-regulated system can provide a potential application for detection/binding of biological analytes and redox-controlled drug release.