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

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ORIGINAL ARTICLE

PBX1 Increases the Radiosensitivity of Oesophageal Squamous Cancer by Targeting of STAT3 Dingyue Yu 1 & Yuanyuan Ma 1 & Chen Feng 2 & Zhiyu Ma 1 & Jiayou Guo 1 & Hui Chen 3 & Tianli He 4 & Jiayi Guo 1 & Xingbang Sun 1 & Qin Qin 3 & Xinchen Sun 3 & Jianxin Ma 1 Received: 20 December 2018 / Accepted: 4 March 2020 # Arányi Lajos Foundation 2020

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 pSTAT3. 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. Keywords Oesophageal squamous cancer . PBX1 . Radiosensitivity . STAT3

Introduction Oesophageal cancer is a common malignant tumour. Worldwide, there are more than 400,000 new oesophageal cancer patients each year, and the incidence rate and mortality of oesophageal cancer rank sixth and eighth among malignant tumours, respectively, worldwide [1–3]. Pathologically, oesophageal cancer involves the following two main types: oesophageal squamous cell carcinoma (OSCC) and oesophageal Dingyue Yu and Yuanyuan Ma contributed equally to this work. * Jianxin Ma [email protected] 1

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

2

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

3

Department of radiotherapy, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, Jiangsu, China

4

Department of Respiratory, Changxing People’s Hospital, Huzhou 313000, Zhejiang, China

adenocarcinoma. China is a high-risk area for oesophageal cancer, and the most prevalent pathological type is OSCC, which accounts for more than 90% of cases [4]. Patients with oesophageal cancer usually present with non-specific symptoms during the early stage, leading to disease progression and a missed opportunity for surgical resection. Therefore, radiation therapy is widely used in patients with ad