ArticleOncotarget2014
Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid activity in osteosarcoma.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 29 citations in OpenAlex.
- Therapeutic strategy for cervical gastric-type adenocarcinoma by targeting CLU to relieve CLU-associated stress and sensitize chemotherapy.Precision clinical medicine · 2026Article
- The role and function of CLU in cancer biology and therapy.Clinical and experimental medicine · 2023Review
- The Ins and Outs of Clusterin: Its Role in Cancer, Eye Diseases and Wound Healing.International journal of molecular sciences · 2023Review
- The therapeutic and prognostic role of clusterin in diverse musculoskeletal diseases: a mini review.Physiological research · 2022Review
- Article
- Review
- Myc is a prognostic biomarker and potential therapeutic target in osteosarcoma.Therapeutic advances in medical oncology · 2020Article
- Transcriptional activation of CBFβ by CDK11Cell communication and signaling : CCS · 2019Article
- The role of Clusterin in cancer metastasis.Cancer management and research · 2019Article
- Bone marrow-derived fibroblasts are a functionally distinct stromal cell population in breast cancer.The Journal of experimental medicine · 2018Article
- Induction of Apoptosis and Inhibition of Epithelial Mesenchymal Transition byEvidence-based complementary and alternative medicine : eCAM · 2018Article
- Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDespite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants new strategies still needed to improve overall patient survival. Among new therapeutic approaches, zoledronic acid (ZOL) represents a promising adjuvant molecule to chemotherapy to limit the osteolytic component of bone tumors. However, ZOL triggers the elevation of heat shock proteins (Hsp), including Hsp27 and clusterin (CLU), which could enhance tumor cell survival and treatment resistance. We hypothesized that targeting CLU using siRNA or the antisense drug, OGX-011, will suppress treatment-induced CLU induction and enhance ZOL-induced cell death in osteosarcoma (OS) cells.
methodsThe combined effects of OGX-011 and ZOL were investigated in vitro on cell growth, viability, apoptosis and cell cycle repartition of ZOL-sensitive or -resistant human OS cell lines (SaOS2, U2OS, MG63 and MNNG/HOS).
resultsIn OS cell lines, ZOL increased levels of HSPs, especially CLU, in a dose- and time-dependent manner by mechanism including increased HSF1 transcription activity. The OS resistant cells to ZOL exhibited higher CLU expression level than the sensitive cells. Moreover, CLU overexpression protects OS sensitive cells to ZOL-induced cell death by modulating the MDR1 and farnesyl diphosphate synthase expression. OGX-011 suppressed treatment-induced increases in CLU and synergistically enhanced the activity of ZOL on cell growth and apoptosis. These biologic events were accompanied by decreased expression of HSPs, MDR1 and HSF1 transcriptional activity. In vivo, OGX-011, administered 3 times a week (IP, 20mg/kg), potentiated the effect of ZOL (s.c; 50µg/kg), significantly inhibiting tumor growth by 50% and prolonging survival in MNNG/HOS xenograft model compared to ZOL alone.
conclusionThese results indicate that ZOL-mediated induction of CLU can be attenuated by OGX-011, with synergistic effects on delaying progression of osteosarcoma.
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