Depleting PTOV1 sensitizes non-small cell lung cancer cells to chemotherapy through attenuating cancer stem cell traits

Journal of Experimental & Clinical Cancer Research

Zeyun Mi¹  Hui Wang²  Zhiqiang Wu²  Maobin Meng²  Boyu Zheng²  Zhiyong Yuan²  Jinlin Zhao²  Zhuang Liu²  Xiangli Jiang³ 

[1] Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Tianjin Medical University;Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer;Department of Thoracic Medical Oncology, Tianjin Medical University Cancer Institute & Hospital;

关键词: Non-small cell lung cancer;    PTOV1;    Chemotherapy;    Cancer stem cell;    β-Catenin;   

DOI  :  10.1186/s13046-019-1349-y

来源: DOAJ

【 摘 要 】

Abstract Background Prostate tumor over expressed gene 1 (PTOV1) has been reported as an oncogene in several human cancers. However, the clinical significance and biological role of PTOV1 remain elusive in non-small cell lung cancer (NSCLC). Methods The Cancer Genome Atlas (TCGA) data and NCBI/GEO data mining, western blotting analysis and immunohistochemistry were employed to characterize the expression of PTOV1 in NSCLC cell lines and tissues. The clinical significance of PTOV1 in NSCLC was studied by immunohistochemistry statistical analysis and Kaplan–Meier Plotter database mining. A series of in-vivo and in-vitro assays, including colony formation, CCK-8 assays, flow cytometry, wound healing, trans-well assay, tumor sphere formation, quantitative PCR, gene set enrichment analysis (GSEA), immunostaining and xenografts tumor model, were performed to demonstrate the effects of PTOV1 on chemosensitivity of NSCLC cells and the underlying mechanisms. Results PTOV1 is overexpressed in NSCLC cell lines and tissues. High PTOV1 level indicates a short survival time and poor response to chemotherapy of NSCLC patients. Depleting PTOV1 increased sensitivity to chemotherapy drugs cisplatin and docetaxel by increasing cell apoptosis, inhibiting cell migration and invasion. Our study verified that depleting PTOV1 attenuated cancer stem cell traits through impairing DKK1/β-catenin signaling to enhance chemosensitivity of NSCLC cells. Conclusion These results suggest that PTOV1 plays an important role in the development and progression of human NSCLC and PTOV1 may serve as a therapeutic target for NSCLC patients.

【 授权许可】

Unknown