دورية أكاديمية
Knockdown of PKM2 enhances radiosensitivity of cervical cancer cells
العنوان: | Knockdown of PKM2 enhances radiosensitivity of cervical cancer cells |
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المؤلفون: | Yanzhu Lin, Hui Zhai, Yi Ouyang, Zhiyuan Lu, Chengbiao Chu, Qianting He, Xinping Cao |
المصدر: | Cancer Cell International, Vol 19, Iss 1, Pp 1-12 (2019) |
بيانات النشر: | BMC, 2019. |
سنة النشر: | 2019 |
المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens LCC:Cytology |
مصطلحات موضوعية: | Radiosensitivity, Apoptosis, Cell cycle, Double strand break repair, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671 |
الوصف: | Abstract Background Pyruvate kinase isozyme type M2 (PKM2) catalyzes the final step in glycolysis and has been found to be up-regulated in multiple human malignancies. However, whether PKM2 regulates the radiosensitivity of human cervical cancer (CC) remains unknown. Methods The expression of PKM2 in 94 patients with CC in the complete response (CR) and noncomplete response (nCR) groups, was evaluated by immunohistochemistry. The effect of PKM2 inhibition on radiosensitivity, the cell cycle, DNA damage, and apoptosis was evaluated by immunofluorescence analysis, colony formation assay, flow cytometry analysis and Western blotting. Results PKM2 expression was more highly expressed in the nCR group than that in CR group and PKM2 expression was enhanced in CC cells after ionizing radiation (IR). In addition, knockdown of PKM2 combined with IR significantly reduced cell growth, promoted apoptosis, and enhanced radiosensitivity. Additionally, knockdown of PKM2 with IR resulted in increased phosphorylation of DNA repair checkpoint proteins (ATM) and phosphorylated-H2AX. Moreover, knockdown of PKM2 combined with IR significantly increased the expression of cleaved caspase 3 and caspase 9, whereas Bcl2 expression was suppressed. Furthermore, knockdown of PKM2 combined with IR markedly reduced the expression of several cancer stem cell biomarkers in vitro, including NANOG, OCT4, SOX2, and Bmi1. Conclusions The results of our study suggests that PKM2 might be involved in mediating CC radiosensitivity and is identified as a potentially important target to enhance radiosensitivity in patients with CC. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1475-2867 |
Relation: | http://link.springer.com/article/10.1186/s12935-019-0845-7; https://doaj.org/toc/1475-2867 |
DOI: | 10.1186/s12935-019-0845-7 |
URL الوصول: | https://doaj.org/article/6863cce74934485a878c8e15536e2f4a |
رقم الأكسشن: | edsdoj.6863cce74934485a878c8e15536e2f4a |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 14752867 |
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DOI: | 10.1186/s12935-019-0845-7 |