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PBX1 通过靶向 STAT3 增加食管鳞癌细胞的放射敏感性。

PBX1 Increases the Radiosensitivity of Oesophageal Squamous Cancer by Targeting of STAT3.

机构信息

Department of radiotherapy, The Lianyungang municipal oriental Hospital Affiliated to Bengbu Medical College, 57 Zhonghua West Road, Lianyungang, 222042, Jiangsu Province, China.

Oncology Department, First Hospital of Bengbu Medical College, Bengbu, 233000, AnHui, China.

出版信息

Pathol Oncol Res. 2020 Oct;26(4):2161-2168. doi: 10.1007/s12253-020-00803-5. Epub 2020 Mar 13.

DOI:10.1007/s12253-020-00803-5
PMID:32170580
Abstract

The radioresistance of oesophageal squamous cell carcinoma (OSCC) is a critical factor leading to a poor prognosis among patients. The expression of PBX1 is abnormally high in a broad range of human tissues, and this gene plays a key role in tumour proliferation. This research intended to explore the radiosensitization of OSCC by silencing PBX1. The OSCC cell lines KYSE450 and KYSE150 were subjected to PBX1 silencing and/or irradiation (IR). Cell proliferation, colony formation, and apoptosis were tested to evaluate the radiosensitization ability of PBX1 silencing. The levels of STAT3 and p-STAT3 in the OSCC cells were tested by Western blotting. Furthermore, KYSE150 cells with or without PBX1 silencing were xenografted into nude mice with or without radiation exposure. Concomitant PBX1 silencing and IR can obviously suppress growth and enhance radiosensitivity in OSCC cells and xenografts. Moreover, the downregulation of PBX1 inhibits the expression of STAT3 and p-STAT3. The downregulation of PBX1 may increase radiosensitivity in OSCC cells and xenografts via the PBX1/STAT3 pathway. Our findings demonstrate that PBX1 may be a potential target for promoting the effect of radiation therapy in OSCC patients.

摘要

食管鳞状细胞癌(ESCC)的放射抵抗性是导致患者预后不良的关键因素。 PBX1 在广泛的人类组织中表达异常升高,该基因在肿瘤增殖中起关键作用。本研究旨在通过沉默 PBX1 来探索 ESCC 的放射增敏作用。 ESCC 细胞系 KYSE450 和 KYSE150 被进行 PBX1 沉默和/或照射(IR)。 通过细胞增殖、集落形成和细胞凋亡实验来评估 PBX1 沉默的放射增敏能力。 通过 Western blot 检测 OSCC 细胞中 STAT3 和 p-STAT3 的水平。 此外, 将具有或不具有 PBX1 沉默的 KYSE150 细胞移植到裸鼠中,并进行或不进行放射暴露。 同时沉默 PBX1 和 IR 可明显抑制 ESCC 细胞和异种移植物的生长,并增强放射敏感性。 此外, PBX1 的下调抑制了 STAT3 和 p-STAT3 的表达。 PBX1 的下调可能通过 PBX1/STAT3 通路增加 ESCC 细胞和异种移植物的放射敏感性。 我们的研究结果表明, PBX1 可能是促进 OSCC 患者放射治疗效果的潜在靶点。

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