Krüppel‐like factor 4 promotes high‐mobility group box 1‐induced chemotherapy resistance in osteosarcoma cells

Huang, Jun; Liu, Ke; Song, Deye; Ding, Muliang; Wang, Junjie; Jin, Qing; Ni, Jiangdong

doi:10.1111/cas.12864

Cited by 26 publications

(23 citation statements)

References 28 publications

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“…It is important to induce cell apoptosis and sensitize resistant osteosarcoma cells in osteosarcoma therapies [49, 50]. Recently, new agents have been gradually reported by different groups of researchers.…”

Section: Programmed Cell Death In the Treatment Of Osteosarcomamentioning

confidence: 99%

Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

Yang

et al. 2016

Oncotarget

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Osteosarcoma is the most common primary bone tumor in children and adolescents. Although combined therapy including surgery and multi-agent chemotherapy have resulted in great improvements in the overall survival of patients, chemoresistance remains an obstacle for the treatment of osteosarcoma. Molecular targets or effective agents that are actively involved in cell death including apoptosis, autophagy and necroptosis have been studied. We summarized how these agents (novel compounds, miRNAs, or proteins) regulate apoptotic, autophagic and necroptotic pathways; and discussed the current knowledge on the role of these new agents in chemotherapy resistance in osteosarcoma.

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Section: Programmed Cell Death In the Treatment Of Osteosarcomamentioning

confidence: 99%

Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

Yang

et al. 2016

Oncotarget

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“…Osteosarcoma mostly develops from mesenchymal stem cells with osteogenic potential, with strong invasion and distal metastatic properties. However, the clinical and histological response rates in osteosarcoma are 56.8 and 47.6%, respectively, which need further improvement (Bouralexis et al, 2003;Huang et al, 2015). Highly malignant and metastatic osteosarcoma usually has poor prognosis, even after comprehensive treatments including surgery, chemotherapy, and radiotherapy Yu et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Among these, cisplatin causes relatively less side effects and has gained increased popularity. However, the clinical and histological response rates in osteosarcoma are 56.8 and 47.6%, respectively, which need further improvement (Bouralexis et al, 2003;Huang et al, 2015). In addition, osteosarcoma tends to develop drug resistance to cisplatin after chronic use, resulting in the failure of treatment.…”

Section: Introductionmentioning

confidence: 99%

The induction of ferroptosis by impairing STAT3/Nrf2/GPx4 signaling enhances the sensitivity of osteosarcoma cells to cisplatin

Liu

Wang

2019

Cell Biology International

205

135

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Recent studies have indicated that promoting ferroptosis is a promising approach to attenuate drug resistance of cancer cells. Hence, this study aimed to induce ferroptosis in osteosarcoma cells, thereby increasing the sensitivity to cisplatin. Osteosarcoma cells MG63 and Saos-2 were incubated with increasing doses of cisplatin to generate cisplatin-resistant strains, MG63/DDP and Saos-2/DDP. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry assays were performed to evaluate cell proliferation and cell death, respectively. Malondialdehyde (MDA), reactive oxygen species (ROS), and lipid oxidation in cells were measured to evaluate the degree of cell ferroptosis. MG63/ DDP and Saos-2/DDP cells showed increased viability and decreased death rate compared with MG63 and Saos-2 cells, respectively, upon cisplatin treatment. Western blotting analysis indicated that protein levels of p-STAT3 (Ser727), nuclear factor erythroid 2-related factor 2 (Nrf2), and glutathione peroxidase 4 (GPx4) in drug-resistant strains increased significantly in response to cisplatin. Co-treatment with cisplatin and agonists of ferroptosis, Erastin, and RSL3, remarkably increased MDA, ROS, lipid oxidation, and sensitivity to cisplatin, in MG63/DDP and Saos-2/DDP cells. Similar results were observed by co-treatment of cells with cisplatin and a STAT3 inhibitor. The reduction of protein levels of p-STAT3 (Ser727), Nrf2, and GPx4 in MG63/DDP and Saos-2/DDP cells resulted in increased ferroptosis and sensitivity to cisplatin. These results indicate that cisplatin-resistant osteosarcoma cells inhibited ferroptosis after exposure to low doses of cisplatin. However, ferroptosis agonists and STAT3 inhibitor reactivated ferroptosis in the cells and consequently increased sensitivity to cisplatin. This study demonstrates a new approach to attenuate resistance of osteosarcoma to cisplatin in vitro.

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“…Osteosarcoma is the most common primary tumor of bone tissue; it is most common in young people and exhibits a high degree of malignancy (1,2). The treatment of osteosarcoma is neoadjuvant chemotherapy and surgery (3).…”

Section: Introductionmentioning

confidence: 99%

Association between expression of nuclear receptor co‑activator 5 protein and prognosis in postoperative patients with osteosarcoma

Dong

et al. 2017

Oncol Lett

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Abstract. The aim of the present study was to investigate the association between the expression of nuclear receptor co-activator 5 protein (NCOA5) and the prognosis of postoperative patients with osteosarcoma. Human osteosarcoma samples were collected from 145 patients and normal bone tissues were collected from 100 individuals as controls. Immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) were employed to measure the levels of NCOA5 protein in cases of human osteosarcoma. The results from the RT-PCR analysis demonstrated that the positive rate of NCOA5 mRNA expression in human osteosarcoma was 17.24% (25/145). The positive rate in normal bone tissues was 84.00% (84/100), which was significantly higher compared with that of human osteosarcoma tissues (χ 2 =33.166; P<0.001). IHC staining indicated that the positive rate of NCOA5 protein in the osteosarcoma samples was 26.21% (38/145). The positive rate in normal bone tissues was 82.00% (82/100), which was significantly increased compared with that of human osteosarcoma tissues (χ 2 =28.166; P<0.001). NCOA5 mRNA and protein expression levels were consistent in human osteosarcoma tissues, and were lower than in control tissues. The expression of NCOA5 was low in human osteosarcoma tissues, while it was high in normal bone tissues. These low NCOA5 expression levels were associated with postoperative survival of human osteosarcoma.

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Krüppel‐like factor 4 promotes high‐mobility group box 1‐induced chemotherapy resistance in osteosarcoma cells

Cited by 26 publications

References 28 publications

Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

Cell apoptosis, autophagy and necroptosis in osteosarcoma treatment

The induction of ferroptosis by impairing STAT3/Nrf2/GPx4 signaling enhances the sensitivity of osteosarcoma cells to cisplatin

Association between expression of nuclear receptor co‑activator 5 protein and prognosis in postoperative patients with osteosarcoma

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