Polydatin inhibits proliferation and promotes apoptosis of doxorubicin-resistant osteosarcoma through LncRNA TUG1 mediated suppression of Akt signaling
| Autor: | Huafang Su, Zhenghua Fei, Liting Chen, Tongzhou Hu, Raoying Xie |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Time Factors Mice Nude Apoptosis Bone Neoplasms Toxicology 03 medical and health sciences 0302 clinical medicine Glucosides Downregulation and upregulation In vivo Cell Line Tumor Stilbenes medicine Animals Humans Protein kinase B Cell Proliferation Pharmacology Mice Inbred BALB C Osteosarcoma Antibiotics Antineoplastic Dose-Response Relationship Drug Cell growth Chemistry medicine.disease Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays Tumor Burden Gene Expression Regulation Neoplastic Blot 030104 developmental biology Doxorubicin Drug Resistance Neoplasm Cell culture 030220 oncology & carcinogenesis Cancer research RNA Long Noncoding Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Toxicology and Applied Pharmacology. 371:55-62 |
| ISSN: | 0041-008X |
| DOI: | 10.1016/j.taap.2019.04.005 |
| Popis: | Background Development of doxorubicin-resistance is the main difficulty for osteosarcoma treatment. LncRNA Taurine upregulated gene 1 (TUG1) has been identified as oncogenic lncRNA in different types of carcinomas and was involved in chemoresistance. We aim to evaluate the anti-proliferative effects and the underlying molecular mechanism of Polydatin in doxorubicin-resistant osteosarcoma. Methods Doxorubicin-resistant osteosarcoma cell lines were established. MTT, colony formation, apoptosis assay, qRT-PCR and Western blotting analysis, immunohistochemistry and animal study were carried out. Results It has been showed Polydatin (50–250 μM) inhibited the cell proliferation in a dose- and time-dependent manner at 24 h, 48 h, and 72 h. Polydatin promoted the cell apoptosis significantly with the highest apoptosis rate >50%. Polydatin down-regulated TUG1 expression and TUG1/Akt signaling suppression was involved in Polydatin treated doxorubicin-resistant osteosarcoma cells. The in vivo study further confirmed the anti-cancer effect of Polydatin and related mechanisms. Conclusions Polydatin may be a novel therapeutic agent for doxorubicin-resistant osteosarcoma treatment and TUG1 would be a potential molecular target. |
| Databáze: | OpenAIRE |
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