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Peng L.,Wenzhou Medical College | Peng L.,Affiliated Hospital of Hainan Medical College | Liu A.,First Peoples Hospital of Yueyang | Shen Y.,Wenzhou Medical College | And 9 more authors.
Oncology Reports | Year: 2013

Thymoquinone (TQ), the predominant bioactive constituent derived from the medicinal spice Nigella sativa (also known as black cumin), has been applied for medical purposes for more than 2,000 years. Recent studies reported that thymoquinone exhibited inhibitory effects on the cell proliferation of several cancer cell lines. This study was performed to investigate the antitumor and anti-angiogenic effects of thymoquinone on osteosarcoma in vitro and in vivo. Our results showed that thymoquinone induced a higher percentage of growth inhibition and apoptosis in the human osteosarcoma cell line SaOS-2 compared to that of control, and thymoquinone significantly blocked human umbilical vein endothelial cell (HUVEC) tube formation in a dose-dependent manner. To investigate the possible mechanisms involved in these events, we performed electrophoretic mobility shift assay (EMSA) and western blot analysis, and found that thymoquinone significantly downregulated NF-κB DNA-binding activity, XIAP, survivin and VEGF in SaOS-2 cells. Moreover, the expression of cleaved caspase-3 and Smac were upregulated in SaOS-2 cells after treatment with thymoquinone. In addition to these in vitro results, we also found that thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing NF-κB and its regulated molecules. Collectively, our results demonstrate that thymoquinone effectively inhibits tumor growth and angiogenesis both in vitro and in vivo. Moreover, inhibition of NF-κB and downstream effector molecules is a possible underlying mechanism of the antitumor and anti-angiogenic activity of thymoquinone in osteosarcoma. Source


Liu C.,Shanghai University | Yin Q.,First Peoples Hospital of Yueyang | Li L.,Yueyang Second Peoples Hospital | Jiao G.,Peking University | And 2 more authors.
Critical Reviews in Eukaryotic Gene Expression | Year: 2013

The XRCC1 Arg194Trp and Arg280His polymorphisms were likely to be involved with the development of bladder cancer. However, there had been inconsistent reports of association. This meta-analysis of literatures was performed to draw a more precise estimation of the relationship. We systematically searched PubMed, Embase, and Web of Science for relevant articles with a time limit of April 25, 2013. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association between the two polymorphisms and bladder cancer susceptibility using a random-effects model. This meta-analysis including 14 case-control studies evaluated the associations between the two XRCC1 polymorphisms and bladder cancer susceptibility. Overall, for Arg194Trp, significant associations were found in TT versus CC (OR = 1.78, 95% CI = 1.12-2.82) and the recessive model (OR = 1.71, 95% CI = 1.11-2.65); for Arg280His, significant associations were also found in AG versus GG (OR = 1.63, 95% CI =1.24-2.13) and the dominant model (OR =1.39, 95% CI = 1.07-1.82). When stratified by ethnicity, in Asian population, significant associations were found for Arg194Trp polymorphism in TT versus CC (OR = 2.99, 95% CI = 1.48-6.06), the dominant model (OR = 1.33, 95% CI = 1.03-1.72) and the recessive model (OR = 2.72, 95% CI = 1.36-5.45), and for Arg280His in GA versus GG (OR = 2.13, 95% CI = 1.63-2.97), but no significant associations were found in no-Asian population. This meta-analysis suggested that XRCC1 Arg194Trp and Arg280His polymorphisms were risk factors for increasing bladder cancer in Asian population. © 2013 Begell House, Inc. Source


Liu A.,University of South China | Huang W.,University of South China | Zeng G.,University of South China | Zhou X.,First Peoples Hospital of Yueyang | And 3 more authors.
Molecular Medicine Reports | Year: 2014

Nasopharyngeal carcinoma (NPC) has a highly increased incidence rate (20/100,000) in Southern regions of China, while being rare in the rest of the world. NPC is a malignant type of cancer due to its high occurrence rate of metastasis; however, biomarkers for effective diagnosis and treatment are yet to be identified. Annexin A1 is a glucocorticoid-regulated member of a large superfamily of calcium and phospholipid-binding proteins and has been shown to have important roles in tumor development and progression, and was demonstrated to be a prognostic biomarker for head and neck cancer types. A previous study by our group showed that Annexin A1 was decreased in NPC tissue as compared with normal adjacent tissue. To investigate whether Annexin A1 is a potential biomarker for NPC, the present study assessed the effect of the Annexin A1 on the biological behavior (i.e., invasion and metastasis) of the highly metastatic NPC cell line 5-8F and the non-metastatic NPC cell line 6-10B. The expression levels of Annexin A1 in the above two cell lines were determined by western blot analysis. Next, the recombinant plasmid pEGFP-C1-Annexin A1 and the small interfering (si)RNA plasmid pRNAT-U6.1-Annexin A1 were used and stably transfected into 5-8F and 6-10B cells, respectively. These established recombinant cell lines were then used to study the up- and downregulation of Annexin A1, respectively. The correlation of Annexin A1 expression levels with the biological behavior of NPC cell lines was analyzed using a cell proliferation assay, flow cytometry, soft agar colony formation assay, as well as Transwell invasion and migration assays. The results demonstrated that upregulation of Annexin A1 suppressed the proliferation, invasion and migration of NPC cells, while downregulation of Annexin A1 promoted the proliferation, invasion and migration of NPC cells. These findings suggested that Annexin A1 may be a potential biomarker for the development and prognosis of NPC, and its dysregulation may have an important role in its underlying pathogenesis. Source


Wu Z.,Wenzhou University | Cai X.,First Peoples Hospital of Yueyang | Huang C.,First Peoples Hospital of Yueyang | Xu J.,First Peoples Hospital of Yueyang | Liu A.,First Peoples Hospital of Yueyang
Oncology Reports | Year: 2016

Angiogenesis is a key factor in the growth and dissemination of malignant diseases, including breast cancer, with significant implications for its clinical management. It is known that microRNAs (miRNAs) play important roles in regulating tumor properties in cancers. However, whether miR-497 contributes to breast cancer angiogenesis remains unknown. Our study demonstrated that miR-497 was significantly downregulated in breast cancer tissue samples and cell lines. Conditioned medium obtained from breast cancer cell line MCF-7, treated with miR-497 mimics, suppressed the proliferation and tube formation of human umbilical vein endothelial cells in vitro, in comparison with the untransfected cells or cells transfected with the control vector alone. Furthermore, western blot assay confirmed that the overexpression of miR-497 reduced VEGF and HIF-1α protein levels. In addition, stable transfection of miR-497 inhibited tumorigenicity and angiogenesis in vivo. Moreover, HIF-1α was also increased in the breast cancer cells under a hypoxic condition, while the ectopic expression of miR-497 partially restored its level. Taken together, our findings indicate that miR-497 is a potential target for the biological therapy of breast cancer. Moreover, miR-497 inhibited the growth of tumors and reduced angiogenesis in a nude mouse xenograft tumor model, which was probably caused by the downregulation of pro-angiogenic molecules, such as VEGF and HIF-1α. Source


Shen E.-D.,First Peoples Hospital of Yueyang | Liu B.,Central South University | Yu X.-S.,Qianfou Mount Hospital of Shandong Province | Xiang Z.-F.,Ningbo Medical Treatment Center Lihuili Hospital | Huang H.-Y.,First Peoples Hospital of Yueyang
OncoTargets and Therapy | Year: 2016

Objective: The aim of this study was to investigate the association between miR-1207-5p expression in peripheral blood and the chemosensitivity of primary gallbladder carcinoma (PGBC). Methods: A total of 85 patients with PGBC undergoing preoperative chemotherapy were divided into effective (n=18) and ineffective (n=67) groups. Another 70 healthy individuals were selected as the control group. An miR-1207-5p mimic (mimic group), an inhibitor (inhibitor group), and a negative control (NC group) sequence were transfected into human gallbladder carcinoma GBC-SD cells. Real-time quantitative polymerase chain reaction was used to determine miR-1207-5p expression. After 48 hours of cisplatin treatment, CCK-8 method was used to detect cell proliferation and flow cytometry were performed to examine cell apoptosis. Results: miR-1207-5p expression in peripheral blood was significantly associated with tumor node metastasis staging of PGBC (P<0.05). Before chemotherapy, miR-1207-5p expression in patients was higher than in healthy individuals (P<0.05). After chemotherapy, the effective group had lower miR-1207-5p expression than the ineffective group (P<0.05). The rates of positive expression of Ki67 protein in the effective group were significantly lower than those in the ineffective group (P<0.05). Receiver operating characteristic curves showed that the area under curve, sensitivity, and specificity of miR-1207-5p used to diagnose PGBC were 0.898, 77.6%, and 97.1% at a cutoff of 1.470, respectively. After 48 hours of cisplatin treatment, compared with the NC group and nontransfected (non-T) group, the mimic group had decreased rates of cell inhibition and apoptosis, but the inhibitor group had increased rates (all P<0.05). The expression levels of caspase3 protein were increased in the mimic group and decreased in the inhibitor group. Cell survival rates in the mimic group at different time points after cisplatin treatment were significantly higher than the corresponding rates in the NC and non-T groups, whereas the cell survival rates in the inhibitor group were significantly lower than the rates in the NC and non-T groups (all P<0.05). The concentration and action time of cisplatin were negatively associated with the cell survival rate in each group (all P<0.05). Conclusion: Cisplatin-based chemosensitivity of PGBC increased as expression of miR-1207-5p in peripheral blood declined. Thus, miR-1207-5p appears to be a promising and novel chemosensitizer for the treatment of PGBC. © 2016 Shen et al. Source

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