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靶向 CDK9:子宫内膜癌治疗的新生物标志物。

Targeting CDK9: A novel biomarker in the treatment of endometrial cancer.

机构信息

Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, P.R. China.

Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410000, P.R. China.

出版信息

Oncol Rep. 2020 Nov;44(5):1929-1938. doi: 10.3892/or.2020.7746. Epub 2020 Sep 1.

Abstract

Endometrial cancer is one of the three major malignant tumors of the female reproductive system. Although cyclin‑dependent kinase 9 (CDK9) has a definitive pathogenic role in various types of cancer, little is known concerning its function in endometrial cancer. Our study was conducted to evaluate the expression and therapeutic potential of CDK9 in endometrial cancer. CDK9 expression was determined by immunohistochemistry in endometrial cancer tissues constructed with paired primary, metastatic, and recurrent tumor tissues from 32 endometrial cancer patients. Small interfering RNA (siRNA) and inhibitors of CDK9 were used to evaluate the effect of CDK9 inhibition on the anti‑apoptotic activity and proliferation in endometrial cancer cells. Colony formation assay and wound‑healing assays were adopted to assess clonal formation and migratory capacity. The results of the immunohistochemistry demonstrated that CDK9 was highly expressed in the human endometrial cancer cell lines; moreover, it was elevated in metastatic and recurrent endometrial tumor tissue compared when compared with that in patient‑matched primary endometrial tumor tissue. Knockdown of CDK9 with siRNA and inhibition of CDK9 activity with the inhibitor suppressed cell proliferation and promoted apoptosis in endometrial cancer. In conclusion, our results provide evidence that CDK9 may be a potential prognostic biomarker and a promising therapeutic target for the treatment of endometrial cancer in the future.

摘要

子宫内膜癌是女性生殖系统三大恶性肿瘤之一。虽然细胞周期蛋白依赖性激酶 9(CDK9)在各种类型的癌症中具有明确的致病作用,但对于其在子宫内膜癌中的功能知之甚少。我们的研究旨在评估 CDK9 在子宫内膜癌中的表达和治疗潜力。我们通过免疫组织化学法检测了 32 名子宫内膜癌患者配对的原发性、转移性和复发性肿瘤组织中的 CDK9 表达。我们使用小干扰 RNA(siRNA)和 CDK9 抑制剂来评估 CDK9 抑制对子宫内膜癌细胞抗凋亡活性和增殖的影响。集落形成实验和划痕愈合实验用于评估克隆形成和迁移能力。免疫组织化学结果表明 CDK9 在人子宫内膜癌细胞系中高表达;此外,与患者匹配的原发性子宫内膜肿瘤组织相比,转移性和复发性子宫内膜肿瘤组织中 CDK9 的表达升高。用 siRNA 敲低 CDK9 和用抑制剂抑制 CDK9 活性可抑制子宫内膜癌细胞的增殖并促进其凋亡。综上所述,我们的研究结果提供了证据表明 CDK9 可能是一种有前途的治疗靶点,有望成为未来治疗子宫内膜癌的潜在预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c8a4/7551504/da84c33a52ae/OR-44-05-1929-g00.jpg

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