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OBJECTIVE: To investigate the potential anticancer effect of combretastatin A4 liposomes (SSL-CA4) in destruction of vascular mimicry (VM) in MDA-MB-231 breast cancer cells in vitro. METHODS: The in vitro inhibitory effect and blocking woundhealing effect of SSL-CA4 were investigated. The VM destruction of SSL-CA4 was evaluated in three dimensional matrigel culture model in MDA-MB-231 cells. The in vitro inhibitory test showed that the maxium inhibition ratio of SSL-CA4 on MDA-MB-231 cells was close to 50%. SSL-CA4 blocked the wound-healing of MDA-MB-231 cells, which was similar to free CA4. RESULTS: SSL-CA4 could inhibit the formation of VM in vitro via inhibition on the VM channel indicators including hypoxia-inducible factor (HIF-α), vascular endothelial- cadherin (VE-Cad), and matrix metallopeptidases (MMP-2). The inhibition on indicators of SSL-CA4 was significantly higher than CA4 treatment groups (P <0.05). CONCLUSION: SSL-CA4 has significant anticancer activity via inhibition of VM in MDA-MB-231 cell line.
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Objective: To investigate the effects of tumor-associated macrophages on the proliferation, invasion and vasculogenic mimicry of Ewing sarcoma cells, and to explore the involved molecular mechanism. Methods: Human monocytic U937 cells were cultured and induced to differentiate into M2-type macrophages in vitro. The expressions of M2-type macrophages-relative cytokines such as CD68, CD163 and CD206 in U937 cells before and after induction were detected by realtime fluorescent quantitative PCR. Ewing sarcoma A673 and SK-ES-1 cells were co-cultured with the induced U937 cells (macrophages). Then the effects of co-culture with macrophages on the proliferation, invasion and vasculogenic mimicry of Ewing sarcoma cells were performed using CCK-8, Transwell chamber invasion and matrigel tubule formation assays, respectively. The expressions of signal transducer and activator of transcription 3 (STAT3) and its downstream phospho-STAT3 (p-STAT3), matrix metalloproteinase 2 (MMP2) and cyclin D2 (CCND2) in Ewing sarcoma cells co-cultured with macrophages were detected by Western blotting. Results: The expression levels of CD68, CD163 and CD206 in monocytic U937 cells were significantly up-regulated after induction in vitro (all P < 0.01), suggesting that the human monocytic U937 cells were differentiated into M2-type macrophages. After the M2-type macrophages were co-cultured with Ewing sarcoma A673 and SK-ES-1 cells for 48 h, the proliferation ability of A673 and SK-ES-1 cells increased significantly as compared with the un-co-cultured control group (both P < 0.05), the number of A673 and SK-ES-1 cells passing through matrigel increased significantly as compared with the control group (both P < 0.05), the branches of new vascular in co-cultured groups were more than those in control group (both P < 0.05), and the expression levels of STAT3 and its down-stream p-STAT3, CCND2 and MMP2 proteins were up-regulated in A673 and SK-ES-1 cells (all P < 0.01). Conclusion: Co-culturing with tumor-associated macrophages can induce the proliferation, invasion and vascular mimetic formation of Ewing sarcoma cells, which may be mediated by activating the STAT3 signaling pathway in Ewing sarcoma cells.
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?Retinoblastoma is a common eye malignant tumor which has high degree of malignancy.The traditional treatment methods are destructive, and the prognosis is poor. Hypoxia-inducible factor-1αhighly express in retinoblastoma and regulate the development and progression of retinoblastoma ( by influencing the proliferation and differentiation of tumor cells and involving in the generation of vascular mimicry ) . This article reviewed the role of hypoxia inducible factor-1αin the development of retinoblastoma which will initiate a new avenue for the treatment of retinoblastoma.
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Objective To observe the influencing of Yiqi Huayu Jiedu Prescription on the growth of HepG2 nude mice transplantation tumor and the expression of related factors of vascular mimicry. Methods Models of transplanted tumors, which were made by HepG2 cells in nude mice, were randomly divided into 7 groups, Yiqi Huayu Jiedu Prescription group, Astragali Radix group, Curcumae Rhizoma group, Paridis Rhizoma group, Gecko group, cis-platinum group, and model group. Except for the model group, the rest groups were given relevant medicine for intervention. 21 days later. HIF-1α, MMP-2, MMP-9, and E-cad were detected by immunohistochemistry, and Twist1 and Bcl-2 were detected by fluorescence quantitative PCR. Results Compared with the model group, tumor volume in the rest groups decreased (P<0.05), and the effect in the Yiqi Huayu Jiedu Prescription group was more obvious than the Astragali Radix group, Paridis Rhizoma group and Gecko group (P<0.05);The expression of vasculogenic mimicry structure was rare in each group, and the model group and cis-platinum group were the most obvious;Except for the Astragali Radix group, the expressions of HIF-1α, MMP-2, and MMP-9 showed statistical significance compared with model group (P<0.05);The expression of E-cad in the Yiqi Huayu Jiedu Prescription group and Astragali Radix group showed statistical significance (P<0.05);The expression of Bcl-2 in the Yiqi Huayu Jiedu prescription group, Paridis Rhizoma group, and Gecko group decreased significantly compared with the model group (P<0.05);The expression of Bcl-2 in the Yiqi Huayu Jiedu prescription group was much better than the other groups (P<0.05);The expression of Twist1 showed statistical significance in the Yiqi Huayu Jiedu Prescription group, Curcumae Rhizoma group, Paridis Rhizoma group, and cis-platinum group (P<0.05). Conclusion Yiqi Huayu Jiedu Prescription can reduce expression of HIF-1α, Twist1, Bcl-2, MMP-2, and MMP-9, and increase expression of E-cad, thereby inhibiting the formation of vascular mimicry.