Jingjing Wu1, Hao Chen1, Meina Ye1, Bing Wang1, Yuzhu Zhang2, Jiayu Sheng3, Tian Meng1, Hongfeng Chen4. 1. Department of Breast, Longhua Hospital Affiliated to Shanghai University of TCM, Shanghai, 200032, China. 2. Department of Mammary, Disease, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, 510120, China. 3. Department of Breast Surgery, Shanghai Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, 200437, China. 4. Department of Breast, Longhua Hospital Affiliated to Shanghai University of TCM, Shanghai, 200032, China. Electronic address: hongfeng_chen058@126.com.
Abstract
BACKGROUND: Abnormally expressed long non-coding RNA (lncRNA) is associated with the development of breast cancer and multidrug resistance. However, the molecular mechanism by which lncRNA regulates cisplatin (DDP) in triple-negative breast cancer (TNBC) remains unclear. METHODS: DDP resistant cell line MDA-MB-231/DDP was established by gradually increasing doses of DDP. Abnormal expression of lncRNA between MDA-MB-231 and MDA-MB-231/DDP was evaluated with microarray. In addition, cell proliferation was evaluated by CCK-8 and Ki67 assays. Furthermore, cell apoptosis was evaluated by cell apoptosis and TUNEL assays. Western blotting assay was used to detect the protein expression. In vivo animal study was performed finally. RESULTS: HCP5 were significantly decreased in MDA-MB-231/DDP cells compared with MDA-MB-231 cells. Downregulation of HCP5 promoted DDP resistance in MDA-MB-231 cells by inhibiting PTEN expression. In contrast, overexpression of HCP5 reversed DDP resistance in MDA-MB-231/DDP cells by upregulating PTEN. In vivo experiments confirmed that overexpression of HCP5 inhibited DDP resistance in TNBC xenograft. CONCLUSION: We found that downregulation of HCP5 contributed to DDP resistance in TNBC, while overexpression of HCP5 reversed the resistance via upregulating PTEN level. Therefore, DDP combined with overexpression of HCP5 might be considered as a therapeutic approach for the treatment of DDP-resistant TNBC.
BACKGROUND: Abnormally expressed long non-coding RNA (lncRNA) is associated with the development of breast cancer and multidrug resistance. However, the molecular mechanism by which lncRNA regulates cisplatin (DDP) in triple-negative breast cancer (TNBC) remains unclear. METHODS:DDP resistant cell line MDA-MB-231/DDP was established by gradually increasing doses of DDP. Abnormal expression of lncRNA between MDA-MB-231 and MDA-MB-231/DDP was evaluated with microarray. In addition, cell proliferation was evaluated by CCK-8 and Ki67 assays. Furthermore, cell apoptosis was evaluated by cell apoptosis and TUNEL assays. Western blotting assay was used to detect the protein expression. In vivo animal study was performed finally. RESULTS:HCP5 were significantly decreased in MDA-MB-231/DDP cells compared with MDA-MB-231 cells. Downregulation of HCP5 promoted DDP resistance in MDA-MB-231 cells by inhibiting PTEN expression. In contrast, overexpression of HCP5 reversed DDP resistance in MDA-MB-231/DDP cells by upregulating PTEN. In vivo experiments confirmed that overexpression of HCP5 inhibited DDP resistance in TNBC xenograft. CONCLUSION: We found that downregulation of HCP5 contributed to DDP resistance in TNBC, while overexpression of HCP5 reversed the resistance via upregulating PTEN level. Therefore, DDP combined with overexpression of HCP5 might be considered as a therapeutic approach for the treatment of DDP-resistant TNBC.
Authors: Qibo Zhang; Huachang Jiang; Youming Jin; Ning Zhang; Zhihua Mu; Yan Guo; Haitao Li Journal: Am J Transl Res Date: 2021-11-15 Impact factor: 4.060