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RAD51是口腔鳞状细胞癌的一个不良预后标志物和潜在治疗靶点。

RAD51 is a poor prognostic marker and a potential therapeutic target for oral squamous cell carcinoma.

作者信息

Tsai Yu-Fen, Chan Leong-Perng, Chen Yuk-Kwan, Su Chang-Wei, Hsu Ching-Wei, Wang Yen-Yun, Yuan Shyng-Shiou F

机构信息

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.

Department of Hematology and Oncology, E-Da Cancer Hospital, I-Shou University, Kaohsiung, 824, Taiwan.

出版信息

Cancer Cell Int. 2023 Oct 5;23(1):231. doi: 10.1186/s12935-023-03071-w.

DOI:10.1186/s12935-023-03071-w
PMID:37798649
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10552296/
Abstract

OBJECTIVES

RAD51 overexpression has been reported to serve as a marker of poor prognosis in several cancer types. This study aimed to survey the role of RAD51 in oral squamous cell carcinoma and whether RAD51 could be a potential therapeutic target.

MATERIALS AND METHODS

RAD51 protein expression, assessed by immunohistochemical staining, was used to examine associations with survival and clinicopathological profiles of patients with oral squamous cell carcinoma. Lentiviral infection was used to knock down or overexpress RAD51. The influence of RAD51 on the biological profile of oral cancer cells was evaluated. Cell viability and apoptosis after treatment with chemotherapeutic agents and irradiation were analyzed. Co-treatment with chemotherapeutic agents and B02, a RAD51 inhibitor, was used to examine additional cytotoxic effects.

RESULTS

Oral squamous cell carcinoma patients with higher RAD51 expression exhibited worse survival, especially those treated with adjuvant chemotherapy and radiotherapy. RAD51 overexpression promotes resistance to chemotherapy and radiotherapy in oral cancer cells in vitro. Higher tumorsphere formation ability was observed in RAD51 overexpressing oral cancer cells. However, the expression of oral cancer stem cell markers did not change in immunoblotting analysis. Co-treatment with RAD51 inhibitor B02 and cisplatin, compared with cisplatin alone, significantly enhanced cytotoxicity in oral cancer cells.

CONCLUSION

RAD51 is a poor prognostic marker for oral squamous cell carcinoma. High RAD51 protein expression associates with resistance to chemotherapy and radiotherapy. Addition of B02 significantly increased the cytotoxicity of cisplatin. These findings suggest that RAD51 protein may function as a treatment target for oral cancer.

TRIAL REGISTRATION

Number: KMUHIRB-E(I)-20190009 Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, approved on 20190130, Retrospective registration.

摘要

目的

据报道,RAD51过表达在几种癌症类型中是预后不良的标志物。本研究旨在探讨RAD51在口腔鳞状细胞癌中的作用,以及RAD51是否可能成为潜在的治疗靶点。

材料与方法

通过免疫组织化学染色评估RAD51蛋白表达,用于检测其与口腔鳞状细胞癌患者生存率及临床病理特征的相关性。利用慢病毒感染来敲低或过表达RAD51。评估RAD51对口腔癌细胞生物学特性的影响。分析用化疗药物和放疗处理后的细胞活力和凋亡情况。联合使用化疗药物和RAD51抑制剂B02来检测额外的细胞毒性作用。

结果

RAD51表达较高的口腔鳞状细胞癌患者生存率较差,尤其是那些接受辅助化疗和放疗的患者。RAD51过表达促进口腔癌细胞在体外对化疗和放疗的抗性。在RAD51过表达的口腔癌细胞中观察到更高的肿瘤球形成能力。然而,免疫印迹分析中口腔癌干细胞标志物的表达没有变化。与单独使用顺铂相比,联合使用RAD51抑制剂B02和顺铂可显著增强口腔癌细胞的细胞毒性。

结论

RAD51是口腔鳞状细胞癌预后不良的标志物。RAD51蛋白高表达与化疗和放疗抗性相关。添加B02可显著增加顺铂的细胞毒性。这些发现表明RAD51蛋白可能作为口腔癌的治疗靶点。

试验注册

编号:KMUHIRB-E(I)-20190009 高雄医学大学附设医院,高雄,台湾,于2019年1月30日批准,回顾性注册。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c1/10552296/b9ff66e16203/12935_2023_3071_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c1/10552296/83b6b94a2407/12935_2023_3071_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c1/10552296/0dd2d6d667a5/12935_2023_3071_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c1/10552296/cea9daccec9b/12935_2023_3071_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c1/10552296/b9ff66e16203/12935_2023_3071_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c1/10552296/83b6b94a2407/12935_2023_3071_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c1/10552296/0dd2d6d667a5/12935_2023_3071_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c1/10552296/cea9daccec9b/12935_2023_3071_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2c1/10552296/b9ff66e16203/12935_2023_3071_Fig4_HTML.jpg

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