ABSTRACT
Aim of Study: This study is to investigate the effects of a novel peroxisome proliferator-activated receptor (PPAR) α/γ dual agonist TZD18 on cell growth, apoptosis, caspase activity, mitochondrial membrane potential, cytochrome c release, and apoptotic-related protein expression in MKN-45 cells. Materials and Methods: 3-(4, 5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide assay against various human cancer cell lines was performed to investigate the whether TZD18 could in reduce the proliferation rates of cancer cells. The percentages of apoptotic cells and mitochondrial membrane potential level were determined by flow cytometry. The subcellular localization of cytochrome c was examined by immunofluorescence microscopy. Western blotting assay was performed to reveal the expression of apoptosis-related proteins. Results: The results showed that the administration of TZD18 could inhibit the growth of MKN-45 cells in a dose- and time-dependent manner. In addition, the apoptotic ratio increased sharply along with a significant increase of caspase activities, mitochondrial membrane potential, and cytochrome c release following TZD18 exposure. The expression of Bax and p27kip1 increased significantly, whereas the expression level of Bcl-2 protein was downregulated. Conclusion: These results indicated that the administration of PPAR α/γ agonist TZD18 may inhibit cell growth by inducing the apoptotic process in MKN-45 cells
ABSTRACT
@# Objective: To explore the molecular mechanism of miR-17-5p regulating the proliferation and invasion of nasopharyngeal carcinoma cells by regulating the expression of breast cancer metastasis suppressor 1 like (BRMS1-like or BRMS1L) gene. Methods:A total of 40 cases of nasopharyngeal carcinoma tissues and corresponding paracancerous tissues resected from nasopharyngeal carcinoma patients, who were admitted to the General Hospital of Pingdingshan Shenma Medical Group during January 2014 to December 2017, were included in this study; in addition, nasopharyngeal carcinoma cell lines CNE 2, HONE 1, C666-1 and nasopharyngeal immortalized epithelial cell line NP69 were also collected for this study. The expression of miR-17-5p in nasopharyngeal carcinoma tissues and cell lines was detected by qPCR. The targeted relationship between BRMS1L and miR-17-5p was predicted by the StarBase and verified by the Dual luciferase reporter gene assay. Effects of transfection of miR-17-5p mimics and inhibitors on the expression of BRMS1Lin CNE2 cells were detected by WB assay. CCK-8, Transwell and Flow cytometry were used to detect the effects of miR-17-5p/BRMS1L axis on the proliferation, migration, invasion and apoptosis of CNE 2 cells. Results: miR-17-5p was highly expressed in nasopharyngeal carcinoma tissues and cell lines (P<0.05 or P<0.01). Knockdown of miR-17-5p significantly inhibited proliferation, invasion and migration of CNE2 cells but promoted apoptosis (P<0.05 or P<0.01); miR-17-5p targeted BRMS1Land down-regulated its expression. Over-expression of BRMS1Lsignificantly inhibited the proliferation, invasion and migration of CNE2 cells but promoted apoptosis (all P<0.01); while simultaneous over-expression of miR-17-5p and BRMS1L reversed the above effects (all P<0.01). Conclusion: miR-17-5p promoted proliferation, invasion, migration and inhibited apoptosis of CNE 2 cells by down-regulating the expression of BRMS1L.