Tumor multidrug resistance (MDR) has become the major obstacle to cancer chemotherapy. Recent studies suggest that tetramethylpyrazine (TMP) could reverse tumor MDR although the mechanism by which TMP overcomes tumor MDR remains elusive. Therefore, in this study, we examined the effects of TMP on MDR in drug-resistant breast cancer cells and investigated the underlying mechanisms. MCF-7 cells and the derived P-glycoprotein (Pgp) overexpressing MCF-7/dox cells were treated with TMP, and their growth was examined by MTT assay. Doxorubicin accumulation in the cells was evaluated by flow cytometry, and the expression of Pgp was detected by Western blot and RT-PCR analysis. The results showed that TMP increased the intracellular concentration of doxorubicin and inhibited Pgp-mediated efflux of doxorubicin in a dose-dependent manner. Moreover, TMP inhibited the ATPase activity of P-gp and suppressed the expression of Pgp in MCF-7/dox cells. Taken together, these data suggest that TMP has potential application in the treatment of chemotherapy-resistant breast cancer.

Pretreatment serum TMAO level is identified as a new independent prognostic biomarker in patients with colorectal cancer.

BackgroundHigh mobility group-box 3 (HMGB3) has been shown to affect tumor initiation and progression. This research aimed to investigate the role of HMGB3 in gastric cancer (GC) cell proliferation, migration, invasion, chemoresistance, and its potential molecular mechanisms.Material/MethodsGC MGC803 and BGC823 cells were transfected with siRNA targeting the HMGB3 gene. The expressions of HMGB3 protein in MGC803 and BGC823 cells after transfection were detected by Western blot assays. We detected cell proliferation and cell cycle by MTT and flow cytometry assay. Cell migration and invasion were determined by wound scratch and transwell assay. MGC803 and BGC823 cells were treated with various concentrations of oxaliplatin, cisplatin, and paclitaxel. After 24 hours of drug exposure, we performed MTT assays to investigate chemoresistance in both groups. Western blot assays were used to detect related proteins expression.ResultsSilencing of HMGB3 inhibited cell proliferation and induced G0/G1 phase arrest of GC cells partly via modulating p53 and p21 pathways, and downregulating Bcl-2/Bax ratio. RNA interference of HMGB3 inhibited cell invasion and migration by downregulating MMP2 and MMP9. Silencing of HMGB3 enhanced sensitive to cisplatin and paclitaxel, and reduced sensitive to oxaliplatin.ConclusionsThese findings suggest the importance of HMGB3 in the regulation of growth, migration, and apoptosis of GC, improve our understanding of the mechanisms of GC pathogenesis, and may promote the development of novel targeted therapies.

Abstract. Background PI3K/Akt signaling has been shown to be activated in a variety of cancers. However, the correlation between Akt activation and VEGF expression is unclear in colon cancer tissues. This study aimed to investigate the expression and predictive value of phosphorylated Akt (pAkt) and VEGF in colon cancer tissues. The expression of PI3K, pAkt and VEGF was detected by immunohistochemical staining in 60 samples of colon cancer tissues and their corresponding adjacent normal colon tissues. In addition, the correlations between the expression levels of the 3 proteins and the clinicopathological parameters of the colon cancer cases were analyzed. The positive rates of PI3K, pAkt and VEGF expression were 71.7% (43/60), 68.3% (41/60) and 61.7% (37/60) in colon cancer, respectively, which were significantly higher than in adjacent normal colon tissues (P<0.001). Correlation analyses showed that PI3K expression was not significantly associated with the gender or age of the patients, tumor size or differentiation (P>0.05), but was closely associated with serous coat infiltration and lymphatic metastasis of colon cancer (P<0.05). Neither pAkt nor VEGF expression were significantly associated with the gender or age of the patients, or tumor differentiation (P>0.05), but were closely associated with tumor size, serous coat infiltration and lymphatic metastasis of colon cancer (P<0.05). In addition, the expression levels of Pl3K and pAkt were positively correlated with that of VEGF in colon cancer tissues (P<0.05). Our data show a positive correlation between PI3K/Akt activation and VEGF expression in colon cancer tissues and indicate that pAkt is an independent prognostic marker for colon cancer patients.