Purpose: Tumor blood vessels exhibit morphological and functional aberrancies. Its maturity and functionality are closely associated with colon cancer progression and therapeutic efficacy. The direct evidence proving whether oridonin (ORI) has vascular normalization promoting effect from which combination therapies will benefit is still lacking. Methods: We established a subcutaneous xenograft model of human colon cancer. The animals were divided into the Control and ORI-treated groups. Immunohistochemical analysis and TUNEL staining was applied to evaluate the proliferation, apoptosis and angiogenesis. Western blot analysis was employed to characterize the angiogenesis-related factors and JAK2/STAT3 signaling. Then, vascular normalization and macrophage reprogramming were assessed by immunofluorescence analysis. Results: The results showed that ORI obviously reduced tumor growth, diminished the numbers of Ki67 + cells and CD31 + microvessel density, while increased the numbers of TUNEL + cells. The expression levels of VEGF and bFGF proteins were dramatically down-regulated while the angiostatin and endostatin levels were increased in the ORI-treated group. Moreover, ORI therapy remarkably promoted the pericyte coverage of tumor vessels from days 5 to 10, with the highest pericyte coverage rate occurred at day 7. In the time window of vascular normalization, hypoxia of the tumor microenvironment was improved by ORI, the expression of HIF-1a was downregulated. Moreover, CD206 + macrophage cells were diminished in the ORI-treated group. These anticancer effects of ORI maybe partly mediated by suppressing JAK2/STAT3 signaling pathway. Conclusions: These results highlight the potential effect of ORI on anti-angiogenesis and inducing vessel normalization roles of ORI, and probably provide optimum time point for the ORI therapy in conjunction with the chemoradiotherapy or immunotherapy.
The present study aims to investigate the effect of miR-30a on the proliferative and invasive abilities of breast cancer cells, and to observe the role of miR-30a in the pathogenesis of breast cancer. With the increase of pathological grade and malignant degree of breast cancer cells, the miR-30a expression level gradually decreased (P<0.01). Transfection with miR-30a mimic significantly inhibited the proliferative and invasive ability of SK-BR-3 cells (P<0.01), while transfection with anti-miR-30a significantly improved the proliferative and invasive ability of these cells (P<0.01). It was revealed using bioinformatic methods that Snail was the functional target gene of miR-30a, and this was verified by the results of a luciferase reporter gene assay. The results of analysis of Snail expression in breast cancer tissues and breast cancer cells revealed that with the increase in pathological grade and malignant degree of breast cancer cells, Snail expression levels gradually increased (P<0.01). Western blotting revealed that miR-30a significantly inhibited Snail expression in SK-BR-3 cells, upregulated the expression of EMT-associated E-cadherin, and downregulated the expression of EMT-associated N-cadherin and Vimentin. MiR-30a was able to affect the proliferation and invasion of breast cancer cells by regulating Snail expression, and therefore has a regulatory effect on the occurrence and development of breast cancer.
Glioblastoma (GBM) is a highly aggressive central nervous system cancer. Its extracranial metastases have rarely been reported in the past few decades. Moreover, the pathogenesis of extracranial GBM metastases remains unclear. Here, we report a case of pulmonary metastasis in a male Wistar rat of C6 GBM model. This reported Wistar male rat was one of the experimental control group without any other intervention except for C6 GBM cells orthotopic implantation. On postoperative day 15, the animal which was reported in this study showed highly cellular, pleomorphic, tumor with nuclear atypia in the brain (Ki67, approximately 65.7%) and lungs (Ki67, 49.5%). Tumor cells in the lung showed immunoreactivity for glial fibrillary acidic protein. Inflammatory CD68 + cell infiltration, weakly positive E-cadherin, and strongly positive staining for vimentin were observed both in tumors in the brain and lungs. Based on further morphological analysis, we speculate that the potential metastatic route into the lung might be hematogenous metastasis.
Heat shock protein 27 (Hsp27), a member of the heat shock protein (Hsp) family, is critical in the stress response. However, the role of Hsp27 in the pathogenesis of preeclampsia remains unknown. The aim of the present study was to examine effect of downregulation of Hsp27 in proliferation, migration, and invasion in human JAR cells. Materials and Methods: To determine their effect, siRNA interference was used to knock down Hsp27 expression in JAR lines. The effects of transfected cells were screened for HSP27 expression by Western blotting analysis. Cell proliferation determined by CCK-8 assay and cell clonogenic assay. Wound healing assay measured the migration ability. Transwell assay measured migration and invasion ability. Results: Downregulation of Hsp27 inhibits proliferation, migration, and invasion in human choriocarcinoma cell line JAR. Conclusion: The present data suggested that Hsp27 may play an important role in preeclampsia.
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