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电压门控钾通道 Kv1.3 在人骨肉瘤中高度表达,并促进骨肉瘤生长。

Voltage-gated potassium channel Kv1.3 is highly expressed in human osteosarcoma and promotes osteosarcoma growth.

机构信息

Department of Orthopaedics, the Affiliated Southeast Hospital of Xiamen University, Zhangzhou 363000, China.

出版信息

Int J Mol Sci. 2013 Sep 23;14(9):19245-56. doi: 10.3390/ijms140919245.

Abstract

Deregulation of voltage-gated potassium channel subunit Kv1.3 has been reported in many tumors. Kv1.3 promotes tumorigenesis by enhancing cell proliferation while suppressing apoptosis. However, the expression and function of Kv1.3 in osteosarcoma are unknown. In the present study, we detected the expression of Kv1.3 in human osteosarcoma cells and tissues by RT-PCR, Western blot and immunohistochemistry. We further examined cell proliferation and apoptosis in osteosarcoma MG-63 cells and xenografts following knockdown of Kv1.3 by short hairpin RNA (shRNA). We found that Kv1.3 was upregulated in human osteosarcoma. Knockdown of Kv1.3 significantly suppressed cell proliferation and increased apoptosis as demonstrated by enhanced cleavage of poly (ADP-ribose) polymerase (PARP) and the activation of Caspase-3/7. Furthermore, adenovirus delivered shRNA targeting Kv1.3 significantly inhibited the growth of MG-63 xenografts. Taken together, our results suggest that Kv1.3 is a novel molecular target for osterosarcoma therapy.

摘要

电压门控钾通道亚基 Kv1.3 的失调控已在许多肿瘤中被报道。Kv1.3 通过增强细胞增殖而抑制细胞凋亡促进肿瘤发生。然而,Kv1.3 在骨肉瘤中的表达和功能尚不清楚。在本研究中,我们通过 RT-PCR、Western blot 和免疫组织化学检测了 Kv1.3 在人骨肉瘤细胞和组织中的表达。我们进一步通过短发夹 RNA (shRNA) 敲低 Kv1.3 后检测了骨肉瘤 MG-63 细胞和异种移植物中的细胞增殖和细胞凋亡。结果发现,Kv1.3 在人骨肉瘤中上调。Kv1.3 的敲低显著抑制了细胞增殖,并通过增加多聚(ADP-核糖)聚合酶(PARP)的裂解和 Caspase-3/7 的激活来增加细胞凋亡。此外,靶向 Kv1.3 的腺病毒递送 shRNA 显著抑制了 MG-63 异种移植物的生长。总之,我们的研究结果表明 Kv1.3 是骨肉瘤治疗的一个新的分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e35b/3794831/195025bc939e/ijms-14-19245f1.jpg

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