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Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.
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Aim To investigate the effect of prodigiosin on the proliferation, migration, cell cycle and apopto- sis of adriamycin-resistant breast cancer cell line MCF- 7/ADR.Methods CCK-8, colony formation assay, scratch test and Transwell were used to detect the pro¬liferation and migration of MCF-7/ADR after treatment with different concentrations of prodigiosin.How cy¬tometry and DAP1 staining were used to detect the cell cycle and apoptosis of MCF-7/ADR cell line after treatment with different concentrations of prodigiosin.Western blot was used to detect the effect of prodigiosin on the expression of caspase-3, Bax and Bcl-2 in MCF- 7/ADR cells.Results Prodigiosin inhibited the pro¬liferation and migration of MCF-7/ADR cell line in a concentration- and time-dependent manner ( P <0.05 ).In addition, prodigiosin enhanced the in¬hibitor}' effect of adriamycin on MCF-7/ADR cell line.Prodigiosin arrested MCF-7/ADR cell line cycle in the S phase and induced cell apoptosis in a time- and dose- dependent manner.The percentage of S phase cells treated with 2 mg • L 1 prodigiosin for 48 hours in¬creased to 35.3% , and the apoptotic rate was as high as 64.83% , which were statistically significant com¬pared with the control group ( P < 0.05 ).Prodigiosin could up-regulate the expression of apoptosis protein caspase-3 and Bax and inhibit the expression of Bcl-2 protein in MCF-7/ADK cell.Conclusions Prodigio¬sin can effectively inhibit the proliferation, migration and promote cell apoptosis and regulate cell cycle in adriamvcin-resistant breast cancer cell line MCF-7/ ADR.Prodigiosin can enhance the sensitivity of MCF- 7/ADR cell line to adriamycin.
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AIM:To investigate the expression of long non-coding RNA PVT1 in ovarian cancer and the role of PVT1 in migration and invasion abilities of ovarian cancer cells.METHODS: The expression of PVT1 in ovarian cancer tissue,normal ovarian tissue and different ovarian cancer cell lines was detected by qPCR.Transwell assay was used to de-tect the invasion ability of ovarian cancer cells after PVT1 silencing.The migration ability of the ovarian cancer cells after PVT1 silencing was detected by scratch test.The interaction between PVT1 and microRNA(miR)-551 was analyzed by dual-luciferase reporter assay.The effect of miR-551-inhibitor on the invasion and migration abilities of ovarian cancer cells after PVT1 silencing was detected by Transwell assay and scratch test.The expression of Wnt signaling pathway-related pro-teins was determined by Western blot after PVT1 silencing.The effects of PVT1 silencing on tumor weight and volume of ovarian cancer were examined by subcutaneous tumor transplantation in nude mice.RESULTS:The expression of PVT1 in ovarian cancer tissue was significantly higher than that in normal ovarian tissue(P<0.05).The expression level of PVT1 in ovarian cancer cell line ES-2 was the highest.PVT1 silencing inhibited the invasion and migration abilities of the ovarian cancer cells.After PVT1 silencing,miR-551-inhibitor promoted the invasion and migration abilities of the ovarian cancer cells.The expression of Wnt signaling pathway-related proteins was decreased after PVT1 silencing(P<0.05).Compared with negative control group,the tumor volume and weight in PVT1-siRNA group were significantly decreased(P<0.05). CONCLUSION:PVT1 plays an important role in the development of ovarian cancer.PVT1 regulates the invasion and mi-gration abilities of ovarian cancer cells through Wnt signaling pathway.
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Aim To investigate the effect of Rhein on the movement and invasiveness of human ovarian carci-noma cells with directional high lymphatic metastasis SKOV3-PM4 cells and explore the role of Rac1/LIMK1/cofilin signaling pathway. Methods Migration assay and invasion assay were used to observe the effect of Rhein on the metastatic and invasive ability of SK-OV3-PM4 cells in vitro. The effect of Rhein on the morphology and cytoskeleton ultrastructure of ovarian cancer cells was observed by laser scanning confocal microscope and scanning electron microscope. The protein expression level of Rac1,LIMK1,PAK1 and co-filin were detected by Western blot, respectively. Re-sults Rhein inhibited the abilities of cell invasion and migration of SKOV3-PM4 cells,and the inhibitory rate increased along with the increase of the concentration and treatment duration. After treated with 8. 80 μmol· L-1 ,17. 60 μmol · L-1 , 26. 40 μmol · L-1 of Rhein for 24 h,the abilities of migration and invasion of SK-OV3-PM4 cells were inhibited ( P <0. 05 ); the mor-phology and cytoskeleton ultrastructure of SKOV3-PM4 cells were changed, cellular pseudopod reduced, cell microfilament fractured and its distribution disordered, plasma membrane was uneven and cell gap widened . After treatment of Rhein and Rac1 inhibitor , Rac1 protein expression and the expression of P-LIMK1 , P-PAK1 and P-cofilin notably decreased in a dose-de-pendent manner compared with the control group ( P<0. 05 ) . After Rhein and Rhein plus Rac1 inhibitor treatment ,P-LIMK1, P-cofilin, P-PAK1 protein levels of SKOV3-PM4 cells significantly decreased compared with the control group , and the group of Rac1 inhibi-tor plus Rhein treatment, the phosphorylated protein decreased more significantly ( P <0. 05 ) . After Rac1 activator plus Rhein treatment, phosphorylated protein expression of P-LIMK1 ,P-PAK1 and P-cofilin upregu-lated significantly ( P <0. 05 ) . Conclusions Rhein may be a potential inhibitor of Rac1 and can inhibit the migrating and invasive capabilities of directional high lymphatic metastasis SKOV3-PM4 cells through down-regulating the phosphorylation of Rac1/LIMK1 /cofilin pathway associated protein.
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RAGE (receptor for advanced glycation end products) is a multiligand receptor on the cell surface.Ligand-RAGE inter-actions activate several signal transduction pathways that propa-gate cellular oxidative stress and inflammatory response.RAGE expressed on the CD4 + T cells has been identified as a central transduction receptor which affects the activation,proliferation, migration and differentiation of the cells.In addition,blockade of RAGE suppressed the development of multiple immune-related disorders mediated by CD4 + T cells.These studies highlight the importance of RAGE and its ligands for CD4 + T cells.This arti-cle briefly reviews the role of RAGE and its ligands on the prolif-eration,migration and differentiation of CD4 + T cells and sum-marizes the related research progress.
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Aim To investigate the effect of small inter-ference RNA-mediated silcencing of the Bmi-1 gene on cell invasion and metastasis in human nasopharyngeal carcinoma cell line CNE-1 . Methods Chemically syn-thesized siRNA targeting the Bmi-1 gene was transfect-ed into CNE-1 cells, which had high invasive and me-tastatic potential. The expression of Bmi-1 mRNA and protein were detected by quantative Real-time PCR and Western blot, respectively. The effects of Bmi-1 knockdown on CNE-1 cells migration and invasion were analysied by Transwell migration assay and Matrigel in-vasion assay. Results Transfected with Bmi-1 siRNA significantly down-regulated the expression of Bmi-1 mRNA and protein as compared with the control group. CNE-1 cells transfected with Bmi-1 siRNA had lower levels of invasion and migration capacity than cells in the control group. Conclusion SiRNA-media-ted silencing of the Bmi-1 gene could significantly in-hibit cell migration and invasion in human nasopharyn-geal carcinoma cell line CNE-1 .