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沉默 MTDH 的表达可增加 SKOV3 卵巢癌细胞的放射敏感性,并降低其增殖和转移能力。

Silencing the expression of MTDH increases the radiation sensitivity of SKOV3 ovarian cancer cells and reduces their proliferation and metastasis.

机构信息

Department of Obstetrics and Gynecology, The Second Hospital of Jilin University, Changchun, Jilin 130041, P.R. China.

Department of Ophthalmology, FAW General Hospital, The Fourth Hospital of Jilin University, Changchun, Jilin 130011, P.R. China.

出版信息

Int J Oncol. 2018 Nov;53(5):2180-2190. doi: 10.3892/ijo.2018.4541. Epub 2018 Aug 28.

Abstract

Ovarian cancer has a high mortality rate among women worldwide. Radiotherapy is considered an effective method of ovarian cancer treatment, however, radioresistance presents a challenge. It is necessary to develop techniques that can increase radiosensitivity in ovarian cancer, and gene therapy is a promising option. The aim of the present study was to investigate the effects of metadherin (MTDH) silencing on the radiosensitivity of ovarian cancer. Ovarian cancer tissues (n=273) and normal ovarian tissues (n=277) were used, as were SKOV3 ovarian cancer cells and the immortalized human ovarian epidermal HOSEpiC cell line. MTT, Transwell and wound-healing assays were performed to assess the proliferation, invasion and migration abilities of the SKOV3 cells. Colony-forming assays and flow cytometry were applied to detect the radiosensitivity and apoptosis of the SKOV3 cells. Nude mouse xenograft models were established to evaluate the effect of MTDH gene silencing on tumor growth and the efficacy of radiotherapy. Ovarian cancer, in tissues and cells, was demonstrated to have a high level of MTDH. Additionally, MTDH silencing was found to significantly inhibit proliferation, migration and invasion, and induce apoptosis in SKOV3 cells, and it was suggested that MTDH depletion significantly increased the sensitivity of the SKOV3 cells to X-ray radiation. MTDH silencing enhanced radiosensitivity and delayed tumor growth in the nude mouse xenograft model. Collectively, the results obtained in the present study suggest the potential role of MTDH silencing as a technique for ameliorating radioresistance in ovarian cancer. The present study provides a promising experimental basis for the improvement of ovarian cancer radiotherapy treatment.

摘要

卵巢癌是全球女性死亡率较高的癌症之一。放射治疗被认为是治疗卵巢癌的有效方法,然而,肿瘤的放射抵抗性是一个挑战。因此,有必要开发能够提高卵巢癌细胞放射敏感性的技术,而基因治疗是一种很有前途的选择。本研究旨在探讨沉默 metadherin(MTDH)对卵巢癌细胞放射敏感性的影响。使用了卵巢癌组织(n=273)和正常卵巢组织(n=277),以及 SKOV3 卵巢癌细胞和永生化人卵巢表皮 HOSEpiC 细胞系。通过 MTT、Transwell 和划痕愈合实验评估 SKOV3 细胞的增殖、侵袭和迁移能力。通过集落形成实验和流式细胞术检测 SKOV3 细胞的放射敏感性和细胞凋亡。建立裸鼠异种移植模型,评估 MTDH 基因沉默对肿瘤生长和放射治疗效果的影响。研究表明,卵巢癌组织和细胞中 MTDH 水平较高。此外,沉默 MTDH 可显著抑制 SKOV3 细胞的增殖、迁移和侵袭,并诱导细胞凋亡,且 MTDH 耗竭可显著提高 SKOV3 细胞对 X 射线辐射的敏感性。沉默 MTDH 增强了裸鼠异种移植模型中的放射敏感性并延缓了肿瘤生长。综上所述,本研究结果提示,沉默 MTDH 可能作为一种改善卵巢癌放射抵抗性的技术具有潜在作用。本研究为改善卵巢癌放射治疗提供了有前景的实验基础。

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