RESUMO
Lung adenocarcinoma (LUAD) accounts for ~40% of lung cancer cases, and the 5-year relative survival rate is no more than 1%. Dysregulation of components of striatin-interacting phosphatase and kinase (STRIPAK) complexes is associated with various diseases, including cancer. Striatin-interacting protein 2 (STRIP2), also called Fam40b, has been reported to regulate tumor cell growth and migration. Here, we investigated the role of STRIP2 in LUAD growth, migration and the underlying mechanisms. Analysis of data from The Cancer Genome Atlas database revealed that STRIP2 is highly expressed and predicted poor outcomes in patients with LUAD. Moreover, quantitative RT-PCR (qRT-PCR) analysis revealed that the mRNA expression of STRIP2 is greater in all tested LUAD cells than in a normal lung cell line. To investigate the function of STRIP2, we overexpressed STRIP2 in SPC-A1 cells and depleted STRIP2 in Calu-3 cells. Cell proliferation was evaluated by Cell Counting Kit-8 and colony-forming assays, and Transwell assay was employed to test cell invasion and migration. Our results indicate that STRIP2 depletion suppressed cell proliferation, invasion and migration in Calu-3 cells, and overexpression of STRIP2 had the opposite effects in SPC-A1 cells. Moreover, we discovered that STRIP2 depletion reduced the protein levels of p-Akt and phosphorylated-mammalian target of rapamycin (p-mTOR) in Calu-3 cells, whereas STRIP2 overexpression increased levels of these proteins in SPC-A1 cells. Furthermore, we found that silencing of STRIP2 clearly enhanced protein levels of E-cadherin and reduced levels of N-cadherin, Vimentin and matrix metalloproteinase-9 in Calu-3 cells, whereas overexpression of STRIP2 had the opposite effect in SPC-A1 cells. Our data indicate that STRIP2 promotes the proliferation and motility of LUAD cells, and this may be mediated through the regulation of the Akt/mTOR pathway and epithelial-mesenchymal transition. These results may facilitate the development of therapeutic strategies to treat LUAD.
Assuntos
Adenocarcinoma de Pulmão/metabolismo , Proteínas do Citoesqueleto/genética , Adenocarcinoma/genética , Adenocarcinoma de Pulmão/genética , Caderinas/genética , Caderinas/metabolismo , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteínas do Citoesqueleto/metabolismo , Transição Epitelial-Mesenquimal/genética , Matriz Extracelular/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Pulmão/patologia , Neoplasias Pulmonares/genética , Invasividade Neoplásica/genética , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Vimentina/genéticaRESUMO
Objective: To explore the combined influence of Arisaematis Rhizoma polysaccharide with cisplatin on the proliferation,apoptosis and epithelial mesenchymal transition of breast carcinoma MDA-MB-231 cells. Methods: MDA-MB-231 cells were divided into control group,Arisaematis Rhizoma polysaccharide group( 50 µg / m L),cisplatin group( 5 µg / m L) and combined group( Arisaematis Rhizoma polysaccharide + cisplatin); the cells proliferation were detected by MTT assay, the cells apoptosis were detected by Annexin V / PI flow cytometry, the mRNA expression levels of Vimentin, N-cadherinand E-cadherin were detected by Real time PCR, the levels of Fibronectin( FN) were detected by ELISA,and the levels of Akt and p-Akt were measured by western blotting. Results: The proliferation of MDA-MB-231 cells were inhibited in Arisaematis Rhizoma polysaccharide group, cisplatin group and combined group with a time dependent manner. The early, late apoptosis rate and E-cadherin mRNA level in Arisaematis Rhizoma polysaccharide group, cisplatin group and combined group were higher,while Vimentin,N-cadherin mRNA,FN level and p-Akt / Akt were lower than those in control group( P < 0. 05). Compared with Arisaematis Rhizoma polysaccharide group and cisplatin group, there were higher in the early,late apoptosis rate and E-cadherin mRNA levels, lower the mRNA levels of Vimentin, N-cadherin, FN and p-Akt / Akt in combined group( P <0. 05). Conclusion: Both of Arisaematis Rhizoma polysaccharide and cisplatin can affect the proliferation, apoptosis and epithelial-mesenchymal transition, and inhibit activation of PI3 K / Akt signaling pathway and the combined effect is better.
Assuntos
Transição Epitelial-Mesenquimal , Antígenos CD , Apoptose , Neoplasias da Mama , Caderinas , Linhagem Celular Tumoral , Proliferação de Células , Cisplatino , Humanos , Polissacarídeos , Transdução de SinaisRESUMO
A total of 198 agricultural soil samples were collected from Zhangjiagang and Changshu in Southern Jiangsu for analysis of 13 polychlorinated biphenyls (PCBs) in order to assess the levels of pollution, sources, area distribution, and potential risk for the environment. All methods were rigorously tested and an adequate quality control was ensured. Only one site had no PCBs residues, and the highest total PCBs concentration in the surface soils was 32.83 ng/g. The average concentration in all the soil samples was 4.13 ng/g, signaling low-level pollution. Tetra-, penta-, and hexa-chlorinated biphenyls were dominant species in soil samples, accounting for more than 75% of sigmaPCBs in the soil samples. PCB118 was the most abundant congener in all the samples. The PCB118 was about 20% of sigmaPCBs. The soil organic matter content showed only a weak correlation with the levels of all PCB congeners, in which a better correlation was noted for the more volatile lighter PCB congeners than for the heavier homologues. To a certain extent, the sources and land use seemed to influence the levels of PCBs.