ArticleInternational journal of molecular sciences2021
Suppression of Estrogen Receptor Alpha Inhibits Cell Proliferation, Differentiation and Enhances the Chemosensitivity of P53-Positive U2OS Osteosarcoma Cell.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 10 citations in OpenAlex.
- Heterogeneity-based stratification identifies CKMT2 as a prognostic marker in osteosarcoma.Frontiers in cell and developmental biology · 2026Article
- Evaluating the synergistic effects of cisplatin and tamoxifen in canine osteosarcoma cells.Frontiers in veterinary science · 2026Article
- Global to local burdens, inequalities, and achievable frontiers of child and adolescent malignant neoplasm of bone and articular cartilage across 953 countries and sublocations, 1980-2040, with deep learning-based forecasts.Journal of orthopaedic translation · 2026Article
- Androgen-induced AR-BRD4 transcriptional regulatory complex promotes malignant proliferation of osteosarcoma cells.Cell death discovery · 2025Article
- Involvement ofFrontiers in oncology · 2025Review
- Integrating network pharmacology and transcriptomics to identify solasonine's anti-osteosarcoma targets and experimental validation.Frontiers in oncology · 2025Article
- Exploration of anti‑osteosarcoma activity of asiatic acid based on network pharmacology andOncology reports · 2024Article
- Multi-Anticancer Activities of Phytoestrogens in Human Osteosarcoma.International journal of molecular sciences · 2023Review
- Molecular and Translational Research on Bone Tumors.International journal of molecular sciences · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteosarcoma is a highly malignant musculoskeletal tumor that is commonly noticed in adolescent children, young children, and elderly adults. Due to advances in surgery, chemotherapy and imaging technology, survival rates have improved to 70-80%, but chemical treatments do not enhance patient survival; in addition, the survival rate after chemical treatments is still low. The most obvious clinical feature of osteosarcoma is new bone formation, which is called "sun burst". Estrogen receptor alpha (ERα) is an essential feature of osteogenesis and regulates cell growth in various tumors, including osteosarcoma. In this study, we sought to investigate the role of ERα in osteosarcoma and to determine if ERα can be used as a target to facilitate the chemosensitivity of osteosarcoma to current treatments. The growth rate of each cell clone was assayed by MTT and trypan blue cell counting, and cell cycle analysis was conducted by flow cytometry. Osteogenic differentiation was induced by osteogenic induction medium and quantified by ARS staining. The effects of ERα on the chemoresponse of OS cells treated with doxorubicin were evaluated by colony formation assay. Mechanistic studies were conducted by examining the levels of proteins by Western blot. The role of ERα on OS prognosis was investigated by an immunohistochemical analysis of OS tissue array. The results showed an impaired growth rate and a decreased osteogenesis ability in the ERα-silenced P53(+) OS cell line U2OS, but not in P53(-) SAOS2 cells, compared with the parental cell line. Cotreatment with tamoxifen, an estrogen receptor inhibitor, increased the sensitivity to doxorubicin, which decreased the colony formation of P53(+) U2OS cells. Cell cycle arrest in the S phase was observed in P53(+) U2OS cells cotreated with low doses of doxorubicin and tamoxifen, while increased levels of apoptosis factors indicated cell death. Moreover, patients with ER-/P53(+) U2OS showed better chemoresponse rates (necrosis rate > 90%) and impaired tumor sizes, which were compatible with the findings of basic research. Taken together, ERα may be a potential target of the current treatments for osteosarcoma that can control tumor growth and improve chemosensitivity. In addition, the expression of ERα in osteosarcoma can be a prognostic factor to predict the response to chemotherapy.
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