Effects of shRNA-mediated Silencing of Integrin α9 Expression on Growth and Lung Metastasis of B16F1 Melanoma Cells
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摘要: 目的 观察shRNA干扰整合素α9(ITGA9)的表达对黑色素瘤细胞B16F1的生长和肺转移的影响。方法 用RNA干扰技术下调B16F1中ITGA9的表达,建立小鼠皮下成瘤和肺转移模型,观察肿瘤生长情况,计数肺转移灶数量。结果 ITGA9-shRNA转染组的肿瘤生长速度减慢(P<0.05),实验终点,该组肿瘤平均体积与scramble-shRNA组相比下降36%;肺转移灶数量显著减少(P<0.05)。结论 下调ITGA9的表达可抑制黑色素瘤细胞B16F1在小鼠体内的生长和肺转移。ITGA9可能成为黑色素瘤的治疗靶点。Abstract: Objective To investigate the effects of shRNA-mediated silencing of integrin α9(ITGA9) expression on growth and lung metastasis of B16F1 melanoma cells. Methods ITGA9-shRNA plasmid was used to inhibit the expression of ITGA9 in melanoma cell line B16F1. The effectiveness and feasibility of RNA interference were confirmed by RT-PCR and Western blot. Subcutaneous tumor model and lung metastasis model were successfully established on C57BL/6 mouse for observation of tumor growth and the number of lung metastatic foci. Results Tumor growth was slowed down in ITGA9-shRNA(P<0.05).The ratio of average tumor volume between shRNA group and scramble-shRNA group was decreased by 36%. The number of lung metastatic foci was signifi cantly decreased(P<0.05). Conclusion Down-regulation of ITGA9 could inhibit B16F1 growth and lung metastasis in vivo. ITGA9 may be a promising target of gene therapy for melanoma.
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Key words:
- Integrin α9 /
- shRNA /
- Melanoma /
- B16F1 cells /
- Lung metastasis
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[1] Krissansen GW, Danen EHJ. Integrin superfamily. Encyclopedia of Life Sciences: John Wiley & Sons, Ltd.,www.els.net.2007. [2] Deb M, Sengupta D, Patra SK. Integrin-epigenetics: a system with imperative impact on cancer[J]. Cancer Metastasis Rev,2012,31(1-2): 221-34. [3] Palmer EL, Rüegg C, Ferrando R, et al. Sequence and tissue distribution of the integrin alpha 9 subunit, a novel partner of beta 1 that is widely distributed in epithelia and muscle[J]. J Cell Biol,1993,123(5):1289-97. [4] Nasulewicz-Goldeman A, Uszczyńska B, Szczaurska-Nowak K, et al. siRNA-mediated silencing of integrin β3 expression inhibits the metastatic potential of B16 melanoma cells[J]. Oncol Rep, 20 12,28(5):1567-73. [5] Roy S, Bingle L, Marshall JF, et al. The role of α9β1 integrin in modulating epithelial cell behaviour[J]. J Oral Pathol Med, 20 11,40(10):755-61. [6] Perdih A, Dolenc MS. Small molecule antagonists of integrin receptors[J]. Curr Med Chem,2010,17(22):2371-92. [7] Gupta SK, Oommen S, Aubry MC, et al. Integrin α9β1 promotes malignant tumor growth and metastasis by potentiating epithelialmesenchymal transition[J]. Oncogene,2013,32(2):141-50. [8] Allen MD, Vaziri R, Green M, et al. Clinical and functional signifi cance of α9β1 integrin expression in breast cancer: a novel cell-surface marker of the basal phenotype that promotes tumour cell invasion[J]. J Pathol,2011,223(5):646-58. [9] Arihiro K, Kaneko M, Fujii S, et al. Signifi cance of alpha 9 beta 1 and alpha v beta 6 integrin expression in breast carcinoma[J]. Breast Cancer,2000,7(1):19-26. [10] Gerashchenko GV, Gordiyuk VV, Skrypkina IY,et al. Screening of epigenetic and genetic disturbances of human chromosome 3 genes in colorectal cancer[J]. Ukr Biokhim Zh,2009,81(4):81-7.
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