Inhibitory effect of interferon-α-2b on expression of cyclooxygenase-2 and vascular endothelial growth factor in human hepatocellular carcinoma inoculated in nude mice |
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基金项目: | Supported by Clinical Key Program Point Subject Foundation of Ministry of Public Health, No. 20012434 |
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摘 要: | AIM: To evaluate the effects of interferon-α-2b (IFN- α-2b) on expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human hepatocellular carcinoma (HCC) inoculated in nude mice and to study the underlying mechanism of IFN-α- 2b against HCC growth. METHODS: Thirb/-two nude mice bearing human HCC were randomly divided into four groups (n = 8). On the 10th day after implantation of HCC cells, the mice in test groups (groups A, B and C) received IFN-α- 2b at a serial dose (10000 IU for group A, 20000 IU for group B, 40000 IU for group C sc daily) for 35 d. The mice in control group received normal saline (NS). The growth conditions of transplanted tumors were observed. Both genes and proteins of COX-2 and VEGF were detected by RT-PCR and Western blot. Apoptosis of tumor cells in nude mice was detected by TUNEL assay after treatment with IFN-α-2b. RESULTS: Tumors were significantly smaller and had a lower weight in the IFN-α-2b treatment groups than those in the control group (P 〈 0.01), and the tumor growth inhibition rate in groups A, B and C was 27.78%, 65.22% and 49.64%, respectively. The expression levels of both genes and proteins of COX-2 and VEGF were much lower in the IFN-α-2b treatment groups than in the control group (P 〈 0.01). The apoptosis index (AI) of tumor cells in the IFN-α-2b treatment groups was markedly higher than that in the control group (P 〈 0.01). Group B had a higher inhibition rate of tumor growth, a lower expression level of COX-2 and VEGF and a higher AI than groups A and C (P 〈 0.05), but there was no significant difference between groups A and C. CONCLUSION: The inhibitory effects of IFN-α-2b on implanted tumor growth and apoptosis may be associated with the down-regulation of COX-2 and VEGF expression. There is a dose-effect relationship. The medium dose of IFN-α-2b for inhibiting tumor growth is 20 000 IU/d.
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关 键 词: | 肝细胞癌 干扰素 生长因子 细胞凋亡 |
收稿时间: | 2006 Mar 20 |
Inhibitory effect of interferon-α-2b on expression of cyclooxygenase-2 and vascular endothelial growth factor in human hepatocellular carcinoma inoculated in nude mice |
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Authors: | Bin Cao Xiao-Ping Chen Peng Zhu Lei Ding Jian Guan Zuo-Liang Shi |
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Institution: | Hepatic Surgery Center, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China |
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Abstract: | AIM: TO evaluate the effects of interferon-α-2b (IFN-α-2b) on expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in human hepatocellular carcinoma (HCC) inoculated in nude mice and to study the underlying mechanism of IFN-α-2b against HCC growth.METHODS: Thirty-two nude mice bearing human HCC were randomly divided into four groups (n = 8). On the 10th day after implantation of HCC cells, the mice in test groups (groups A, B and C) received IFN-α-2b at a serial dose (10000 IU for group A, 20000 IU for group B, 40000 IU for group C sc daily) for 35 d. The mice in control group received normal saline (NS). The growth conditions of transplanted tumors were observed. Both genes and proteins of COX-2 and VEGF were detected by RT-PCR and Western blot. Apoptosis of tumor cells in nude mice was detected by TUNEL assay after treatment with IFN-α-2b.RESULTS: Tumors were significantly smaller and had a lower weight in the IFN-α-2b treatment groups than those in the control group (P< 0.01), and the tumor growth inhibition rate in groups A, B and C was 27.78%, 65.22% and 49.64%, respectively. The expression levels of both genes and proteins of COX-2 and VEGF were much lower in the IFN-α-2b treatment groups than in the control group (P<0.01). The apoptosis index (AI) of tumor cells in the IFN-α-2btreatment groups was markedly higher than that in the control group (P<0.01). Group B had a higher inhibition rate of tumor growth, a lower expression level of COX-2 and VEGF and a higher AI than groups A and C (P<0.05), but there was no significant difference between groups A and C.CONCLUSION: The inhibitory effects of IFN-α-2b on implanted tumor growth and apoptosis may be associated with the down-regulation of COX-2 and VEGF expression. There is a dose-effect relationship. The medium dose of IFN-α-2b for inhibiting tumor growth is 20000 IU/d. |
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Keywords: | Hepatocellular carcinoma Cyclooxygenase-2 Vascular endothelial growth factor Apoptosis |
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