ABSTRACT
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of cancers including non-small cell lung cancer (NSCLC). CIP2A plays an 'oncogenic nexus' to participate in the tumorigenesis and chemoresistance in several cancer types. AKT and mTORC1 overactivation are detected in NSCLC and many other cancers. Previous studies found that the CIP2A/AKT/mTOR pathway controls cell growth, apoptosis, autophagy process. Polyphyllin I (PPI) and polyphyllin VII (PPVII) are natural components extracted from Paris polyphylla that display anti-cancer properties. In the present study, we investigated whether PPI and PPVII can be used in the cisplatin (DDP)-resistant human NSCLC cell line A549/DDP. Results demonstrated that PPI and PPVII treatment significantly suppressed A549/DDP cell proliferation, migration, invasion and EMT, induced apoptosis and autophagy. Further examination of the mechanism revealed that the PPI and PPVII significantly upregulated the p53, induced caspase-dependent apoptosis and suppressed the CIP2A/AKT/mTOR pathway. The activation of autophagy was mediated through PPI and PPVII induced inhibition of mTOR. We propose that PPI and PPVII might be developed as candidate drugs for DDP-resistant NSCLC.
ABSTRACT
AIM:To investigate the effects of cancerous inhibitor of protein phosphatase 2A (CIP2A) over-ex-pression on the proliferation and apoptosis of gastric epithelial cells .METHODS:The mRNA expression of CIP2A and cy-clin D1 in the tissues of normal gastric mucosa and gastric polyps was detected by RT -qPCR.The GES-1 cells were divided into control group, Ad-emp group and Ad-CIP2A group.The cell proliferation ability was detected by MTT assay and BrdU assay , and the cell apoptosis was analyzed by flow cytometry .The expression of apoptosis-related molecules was determined by Western blot and RT-qPCR.The levels of inflammatory cytokines were measured by ELISA after GES-1 cells were infec-ted with Ad-emp and Ad-CIP2A.Furthermore, the protein levels of p-Rb, E2F1 and cyclin D1 in the GES-1 cells was de-termined by Western blot after transfected with E2F1 siRNA.RESULTS:The expression of CIP2A and cyclin D1 in ade-nomatous gastric polyps tissues was significantly higher than that in normal gastric mucosa tissues , and no significant change of that between hyperplastic gastric polyps tissues and normal gastric mucosa was observed .After transfected with CIP2A, the proliferation ability of GES-1 cells was increased , the cell apoptosis was inhibited , the concentrations of IL-1βand IL-10 was up-regulated and the protein levels of p-Rb, E2F1 and cyclin D1 were increased, while the protein levels of p-Rb, E2F1 and cyclin D1 were significantly decreased after transfected with E2F1 siRNA.CONCLUSION: CIP2A promotes the proliferation and inhibits the apoptosis of GES-1 cells by activating Rb/E2F1.
ABSTRACT
Objective To study the different expressions of cancerous inhibitor of protein phosphatase 2A (CIP2A)in non-small cell lung cancer (NSCLC),investigate its clinical significance and potential prognostic value.Methods Immunohistochemical and real-time polymerase chain reaction (PCR)were used to detect the expressions of CIP2A mRNA and protein in two groups of sixty paired NSCLC specimens and adjacent non-cancer tissues.The relationship between its expression and clinical pathological data and prognostic factors were analysed. Results The expression of CIP2A mRNA in NSCLC specimens was higher than those in adjacent non-cancer tissues(P<0.01 );The expression of CIP2A protein in NSCLC tissues was significantly higher than that in the corresponding adjacent non-cancer tissues (P<0.01 ).The expression of CIP2A was closely correlated with the differentiation and lymph node metastasis of NSCLC tissues (P<0.05 ),while incorrelated with sex,age,pathematology type,tumor size and tumor node metastasis (TNM)stage.Conclusion CIP2A highly expresses in NSCLC,and the expression of CIP2A will increase with the differentiation and lymph node metastasis of NSCLC tissues.The expression of CIP2A and lymph node metastasis can be used as an independent risk factor for the prognosis of patients with NSCLC.
ABSTRACT
Objective: To investigate the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) in non-small cell lung cancer (NSCLC) tissues and its clinical significance. Methods: The expressions of CIP2A protein in NSCLC tissues and their corresponding para-cancerous tissues from 97 cases of NSCLC were detected by immunohistochemistry. The relationship between the expression of CIP2A protein and the clinicopathological features in patients with NSCLC was analyzed. Results: The positive expression rate of CIP2A protein in NSCLC tissues [76.3% (74/97)] was significantly higher than that in the corresponding para-cancerous tissues [5.2% (5/97)] (P 0.05). The overall survival time of patients with positive expression of CIP2A protein was shorter than that of patients with negative expression of CIP2A protein (P =0.001). The expression of CIP2A protein, TNM stage and the differentiation of tumor were independent prognostic factors of NSCLC (P <0.05). Conclusion: The expression of CIP2A protein is significantly increased in NSCLC tissues, and the positive expression of CIP2A protein is associated with the prognosis of patients with NSCLC. Copyright© 2011 by TUMOR.