14-3-3ζ protein mediates gemcitabine resistance in NK/T-cell lymphoma / 中华血液学杂志

Objective@#To explore the molecular mechanisms of 14-3-3ζ in gemcitabine resistance in extranodal NK/T-cell lymphoma, nasal type (ENKTL) .@*Methods@#The effects of cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and transwell assay. YTS cells were exposed to gradually increased concentrations of gemcitabine to establish gemcitabine-resistant YTS cells (YTS-gem) in vitro. 14-3-3ζ specific siRNA lentiviral vector was transfected into YTS and YTS-gem cells to downregulate 14-3-3ζ expression, and stable transfected cell clones were screened. The protein expression was determined by Western blot.@*Results@#①14-3-3ζ expression was significantly up-regulated in gemcitabine resistant YTS-gem cells, comparing with that of YTS cells (P<0.05) . ②The results of CCK-8 and transwell assay showed that downregulation of 14-3-3ζ significantly reduced the cell proliferation and invasion abilities (P<0.05) . ③Downregulation of 14-3-3ζ could restore gemcitabine sensitivity in gemcitabine resistant YTS-gem cells (P<0.05) . ④Western blotting results showed that knockdown of 14-3-3ζ significantly upregulated pro-apoptotic Bax, and downregulated anti-apoptotic Bcl-2, Caspase-3, cleaved caspase-3, Cyclin D1 in gemcitabine-resistant YTS-gem cells (P<0.05) . There was no significant difference in p53 ang P-gp expression levels.@*Conclusions@#14-3-3ζ was upregulated in gemcitabine resistant YTS cells. Overexpression of 14-3-3ζ promoted cell proliferation and enhanced cell migration. 14-3-3ζ contributed to gemcitabine resistance to ENKTL through anti-apoptosis.

14-3-3ζ protein mediates gemcitabine resistance in NK/T-cell lymphoma / 中华血液学杂志

Objective: To explore the molecular mechanisms of 14-3-3ζ in gemcitabine resistance in extranodal NK/T-cell lymphoma, nasal type (ENKTL) . Methods: The effects of cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and transwell assay. YTS cells were exposed to gradually increased concentrations of gemcitabine to establish gemcitabine-resistant YTS cells (YTS-gem) in vitro. 14-3-3ζ specific siRNA lentiviral vector was transfected into YTS and YTS-gem cells to downregulate 14-3-3ζ expression, and stable transfected cell clones were screened. The protein expression was determined by Western blot. Results: ①14-3-3ζ expression was significantly up-regulated in gemcitabine resistant YTS-gem cells, comparing with that of YTS cells (P<0.05) . ②The results of CCK-8 and transwell assay showed that downregulation of 14-3-3ζ significantly reduced the cell proliferation and invasion abilities (P<0.05) . ③Downregulation of 14-3-3ζ could restore gemcitabine sensitivity in gemcitabine resistant YTS-gem cells (P<0.05) . ④Western blotting results showed that knockdown of 14-3-3ζ significantly upregulated pro-apoptotic Bax, and downregulated anti-apoptotic Bcl-2, Caspase-3, cleaved caspase-3, Cyclin D1 in gemcitabine-resistant YTS-gem cells (P<0.05) . There was no significant difference in p53 ang P-gp expression levels. Conclusions: 14-3-3ζ was upregulated in gemcitabine resistant YTS cells. Overexpression of 14-3-3ζ promoted cell proliferation and enhanced cell migration. 14-3-3ζ contributed to gemcitabine resistance to ENKTL through anti-apoptosis.

14-3-3ζ Overexpression is Associated with Poor Prognosis in Ovarian Cancer

PURPOSE: 14-3-3ζ regulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3ζ is associated with ovarian cancer prognosis. MATERIALS AND METHODS: We examined 14-3-3ζ expression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3ζ expression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTS-based assay following cisplatin treatment. RESULTS: Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3ζ expression, and 14-3-3ζ overexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3ζ overexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3ζ expression group, but not reached in the low 14-3-3ζ expression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3ζ by RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death. CONCLUSION: 14-3-3ζ overexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3ζ could be a therapeutic option that enhances the antitumor activity of cisplatin.

Research progress of the relationship between 14-3-3ζ and malignant tumor / 实用肿瘤学杂志

The 14-3-3 protein is a highly conserved acidic polypeptide family involved in intracellular signaling,protein transportation, cell proliferation, invasion, migration, and apoptosis. Many studies have shown that 14-3-3ζhas a high expression level in many malignant tumors. This paper introduces the structure of 14-3-3ζ,the biological function,and the development of the malignant tumor ( breast cancer,lung cancer,hepatocel-lular carcinoma,glioma,head and neck neoplasms) related to the development of 14-3-3ζand treatment of ma-lignant tumor in order to provide valuable information and ideas.

The expressions of GM130, 14-3-3ζ and integrinβ3 in ovarian epithelial malignant tumor tissues and their clinical significance / 肿瘤

Objective: To investigate the expressions of Golgi matrix protein 130 (GM130), 14-3-3ζ and integrinβ3 in ovarian epithelial malignant tumor tissues and their clinical significance. Methods: The expressions of GM130, 14-3-3ζ and integrinβ3 in 49 ovarian epithelial malignant tumor tissues, 30 ovarian epithelial benign tumor tissues and 23 normal ovarian epithelial tissues were detected by immunohistochemistry. The expression levels of GM130, 14-3-3ζ and integrinβ3 mRNAs and proteins in ovarian epithelial malignant tumor tissues, ovarian epithelial benign tumor tissues and normal ovarian epithelial tissues were detected by RT-PCR and Western blotting, respectively. Results: The positive rates of GM130, 14-3-3ζ and integrinβ3 expressions in ovarian epithelial malignant tumor tissues were higher than those in the ovarian epithelial benign tumor tissues and normal ovarian epithelial tissues (P 0.05). The expression levels of GM130, 14-3-3ζ and integrinβ3 mRNAs and proteins in ovarian epithelial malignant tumor tissues were higher than those in the ovarian epithelial benign tumor tissues and the normal ovarian epithelial tissues (P < 0.05). Conclusion: The high expressions of GM130, 14-3-3ζ and integrinβ3 in ovarian epithelial malignant tumor may play an important role in malignant progression. GM130 may become a prognostic factor and a therapeutic target in patients with ovarian tumors. Copyright© 2014 by TUMOR.