ABSTRACT
This study aimed to investigate the effects of curcumin (Cur) on the proliferation, migration, and invasion of gemcitabine (GEM) resistant lung cancer A549 cells (A549/GEM), and the potential mechanism. After treating with GEM, individually or combined with Cur, the inhibition, migration, and invasion of A549/GEM were tested by the CCK8, transwell, and cell wound healing assays, respectively. QRT-PCR and Western blot were used to detect mRNA and protein markers. Finally, the therapeutic effects of GEM, individually or combined with Cur, were verified in nude mice. The results indicated that the combined application of Cur and GEM can improve the sensitivity of A549/GEM to the GEM. Compared with the GEM, GEM plus Cur significantly decreased the migration and invasion of A549/GEM cells. The expression levels of MMP9 , Vimentin, and N-cadherin were significantly decreased, while the E-cadherin expression was increased. In vivo experiments showed a better therapeutic effect of GEM combined with Cur than that of GEM alone, and the combination therapy did not cause more toxicity to animals. In summary, Cur reversed GEM resistance and inhibited the EMT process in A549/GEM cells. GEM, combined with Cur, is safe and more effective in the treatment of non-small cell lung cancer.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Curcumin , Lung Neoplasms , Animals , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Deoxycytidine/analogs & derivatives , Lung Neoplasms/pathology , Mice , Mice, Nude , GemcitabineABSTRACT
Malignant glioma is one of the most common primary tumors of the central nervous system. MicroRNAs (miRNAs) play an important role in the occurrence of gliomas, and have a potential value in their treatment. In this study, we investigated the effect of miR-1247-5p on glioma progression. miR-1247-5p showed a low expression in glioma cell lines and glioma tissues from patients. The ectopic overexpression of miR-1247-5p significantly inhibited the proliferation and invasion of U251 cells, induced apoptosis in vitro, and inhibited the growth of transplanted tumor cells in vivo CDC14B was found to be a potential target of miR-1247-5p. The overexpression of miR-1247-5p can significantly down-regulate the expression of CDC14B by directly targeting the 3'UTR of this gene. CDC14B can promote the degradation of p53 and inhibit its activity. The downregulation of CDC14B maintained the activity of p53 and inhibited its degradation. These results suggest that miR-1247-5p functions as a tumor suppressor in human astroglioma U251 cells via the miR-1247-5p/CDC14B/p53 signaling axis. These findings indicate that miR-1247-5p has the potential to be a therapeutic target and diagnostic marker for gliomas.
Subject(s)
Astrocytoma/pathology , Biomarkers, Tumor/metabolism , Brain Neoplasms/pathology , Dual-Specificity Phosphatases/metabolism , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Animals , Apoptosis , Astrocytoma/genetics , Astrocytoma/metabolism , Biomarkers, Tumor/genetics , Brain Neoplasms/genetics , Brain Neoplasms/metabolism , Cell Movement , Cell Proliferation , Dual-Specificity Phosphatases/genetics , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Prognosis , Tumor Cells, Cultured , Xenograft Model Antitumor AssaysABSTRACT
Lower serum level of 25-hydroxyvitamin D is associated with several negative outcomes. However, previous studies have indicated that 25-hydroxyvitamin D is associated with lung cancer risk and survival, but presented controversial results.PubMed and Embase databases were searched update to August 2017 to identify and quantify the potential association between 25-hydroxyvitamin D and lung cancer risk and survival.Seventeen eligible studies involving a total of 138,858 participants with 4368 incident cases were included in this meta-analysis. Our results showed statistically significant association between 25-hydroxyvitamin D and lung cancer risk and mortality. However, circulating 25-hydroxyvitamin D was not associated with overall lung cancer survival. Furthermore, compared with the lowest circulating 25-hydroxyvitamin D, the highest circulating 25-hydroxyvitamin D is significantly decreased risk of lung cancer risk in male and female. In addition, the highest circulating 25-hydroxyvitamin D was significantly associated with a lower risk in Caucasian and Asian. We also obtained the best fit at an inflection point of 10 nmol/L in piecewise regression analysis, increasing 10 nmol/L dose of circulating 25-hydroxyvitamin D was associated with an 8% reduction in the risk of lung cancer risk and an 7% reduction in the risk of lung cancer mortality. Subgroup meta-analyses in study quality, number of participants, and number of cases showed consistent with the primary findings.The highest circulating 25-hydroxyvitamin D was associated with decreased lung cancer risk and mortality but not overall survival.
