Objective
To investigate the association between curcumin and the differentially expressed genes (DEG) in synovial tissues of osteoarthritis.
Methods
Microarray analysis was used to screen for the DEG in osteoarthritis synovial cells. Curcumin‐related genes were identified through the drug–gene interaction network STITCH (
http://stitch.embl.de/cgi/input.pl
). Expression levels of fibronectin 1 (FN1) and collagen III protein were measured by western blot. MTT assay was used to examine the effects of different concentrations of curcumin on cell viability. Western blot and quantitative real‐time polymerase chain reaction were used to validate the different expression levels of matrix metalloproteinase‐3 (MMP3). Clone formation assay, flow cytometry, and the TUNEL method were conducted for detecting the cell proliferation and apoptosis rate.
Results
In the two chips of GSE1919 and GSE55235, the average expression of
MMP3
in the osteoarthritis group was 63.7% and 12.9% higher than that of the healthy control, respectively. The results of western blot also showed that the average expression of
MMP3
in 30 osteoarthritis patients was 132% higher than that of the healthy group, which confirmed that
MMP3
was highly expressed in osteoarthritis group. The results of MTT showed that at 72 h, the cell viability of 40 μmol/L curcumin was the lowest and 79.6% lower than for the 0 μmol/L group, so the final curcumin concentration of 40 μmol/L was selected for subsequent experiments. Western blot results further showed that the expression of
MMP3
was 44% lower in the untreated groups compared with the curcumin group, and the expressions of FN1 and collagen III were increased by 112% and 84%, respectively, which indicated that curcumin inhibited
MMP3
expression and decreased osteoarthritis synovial cell activity. Cloning formation experiments showed that cell numbers increased by 75% and 20.5% in untreated and curcumin groups, and compared with the untreated group, the cells in the curcumin group decreased by 30.8%. Flow cytometry showed that the apoptotic rate in the curcumin group increased by 85.1% compared with the untreated group, but for a single group,
MMP3
decreased the apoptotic rate by 53.9% and 46.7%, respectively.
Conclusions
MMP3
was highly expressed in osteoarthritis synovial cells. Curcumin could reduce cell viability, inhibit cell proliferation, increase cell apoptosis, and eventually alleviate inflammation of osteoarthritis by inhibiting the expression of
MMP3.
The aim of this study was to evaluate the value of postoperative adjuvant therapy for resectable thoracic esophageal squamous cell carcinoma (ESCC) in China. We retrospectively analyzed 426 eligible patients seen between October 2007 and November 2011. Specifically, we assessed clinicopathological characteristics and the disease-free and overall survival rates. Of the 426 patients, 272 cases underwent surgery alone, and 154 cases received postoperative adjuvant therapy (67 cases with radiotherapy, 57 cases with chemotherapy, and 30 cases with simultaneous chemoradiotherapy). The median follow-up time was 48.0 months (23.0-72.0 months), and the median survival time was 48.4 months (1.0-72.0 months). We found a significant difference between the surgery-alone and adjuvant therapy groups in the status of lymph node (LN) metastasis (N stage; P < 0.01), but there were no differences between the two groups with regard to other clinicopathological characteristics, including age, sex, lesion location, T stage, differentiation grades, surgery approach, or average number of LN dissections. The 5-year disease-free survival (DFS) rates of the surgery-alone and adjuvant therapy groups were 48.9 and 37.1 %, respectively (P < 0.001); no significant difference was found in 5-year overall survival (OS) rate between the two groups (P > 0.05). A stratification analysis based on N stage suggested that the 5-year DFS and OS rates were similar in N0-N3 subgroups (P > 0.05), except that patients with surgery alone had a higher 5-year DFS than those with postoperative adjuvant therapy in N0 subgroup (P = 0.013). Our data suggest that patients with resectable thoracic ESCC may not benefit from postoperative adjuvant therapy. Further prospective studies are required to elucidate the utility of postoperative adjuvant therapy and to standardize individualized treatments for resectable ESCC.
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