Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0279530 (bone cancer)
 1,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chondrosarcoma is a cartilage tumor and is the second most common malignant bone cancer. Unlike many tumors, chondrosarcomas are resistant to conventional chemotherapy and radiotherapy. Autophagy is a homeostatic mechanism through which cellular proteins and organelles are subjected to lysosomal degradation and recycling. Autophagy could play a dual role in cancer by facilitating either cell death or cell survival. To determine whether autophagy plays a role in cell death in chondrosarcoma, we have studied the effect of the anti-tumor compound 2-methoxyestradiol (2-ME) in chondrosarcoma cells in culture. Transmission electron microscopy imaging indicates that 2-ME treatment leads to the accumulation of autophagosomes in human chondrosarcoma (SW1353 and Hs819T) cells. Also, 2-ME induces the conversion of microtubule-associated protein LC3-I to LC3-II, a protein marker that is correlated with the formation of autophagosomes. Our results show that siRNAs directed against ATG3 blocks 2-ME-induced autophagosome formation in chondrosarcoma cells. In addition, treatment with Bafilomycin A1 (Baf) and 3-methyladenine (3-MA), the inhibitors of autophagy, further increased the cell death in 2-ME-treated chondrosarcoma cells. Taken together, our studies demonstrate that autophagy causes resistance to cytotoxicity in chondrosarcoma cells, and the efficacy and anti-tumor effects of drugs in chondrosarcoma could be enhanced by modulating autophagy.
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PMID:Inhibition of Autophagy Increases 2-Methoxyestradiol-Induced Cytotoxicity in SW1353 Chondrosarcoma Cells. 2633 92

Bone cancer pain (BCP) is one of the most common pains in patients with malignant cancers. The mechanism underlying BCP is largely unknown. Our previous studies and the increasing evidence both have shown that acid-sensing ion channels 3 (ASIC3) is an important protein in the pathological pain state in some pain models. We hypothesized that the expression change of ASIC3 might be one of the factors related to BCP. In this study, we established the BCP model through intrathecally injecting rat mammary gland carcinoma cells (MRMT-1) into the left tibia of Sprague-Dawley female rats, and found that the BCP rats showed bone destruction, increased mechanical pain sensitivities and up-regulated ASIC3 protein expression levels in L4-L6 dorsal root ganglion. Then, resveratrol, which was intraperitoneally injected into the BCP rats on post-operative Day 21, dose-dependently increased the paw withdrawal threshold of BCP rats, reversed the pain behavior, and had an antinociceptive effect on BCP rats. In ASIC3-transfected SH-SY5Y cells, the ASIC3 protein expression levels were regulated by resveratrol in a dose- and time-dependent manner. Meanwhile, resveratrol also had an antinociceptive effect in ASIC3-mediated pain rat model. Furthermore, resveratrol also enhanced the phosphorylation of AMPK, SIRT1, and LC3-II levels in ASIC3-transfected SH-SY5Y cells, indicating that resveratrol could activate the AMPK-SIRT1-autophagy signal pathway in ASIC3-transfected SH-SY5Y cells. In BCP rats, SIRT1 and LC3-II were also down-regulated. These findings provide new evidence for the use of resveratrol as a therapeutic treatment during BCP states.
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PMID:Resveratrol attenuates bone cancer pain through regulating the expression levels of ASIC3 and activating cell autophagy. 2903 49

Osteosarcoma (OS) is the most common type of bone cancer in children and adolescents. LncRNA differentiation antagonizing nonprotein coding RNA (DANCR) has been reported to be aberrant expression in osteosarcoma and contribute to proliferation, migration and invasion of cancer cells. Here, we further explore the exacted molecular mechanism of DANCR in OS. The expression of DANCR, microRNA-216a-5p (miR-216a-5p) and SOX5 was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Cells proliferation and apoptosis were analyzed by WST-1assay or flow cytometry, respectively. The migratory and invasion abilities were measured by transwell assay. Western blot was used to detect the level of SOX5 and autophagy-related protein of Beclin1, LC3-I and LC3-II. The interaction among DANCR, miR-216a-5p and SOX5 was explored by luciferase reporter assay, RIP assay or Pull-down assay. Murine xenograft model was established using 143B cells transfected with sh-DANCR. We found that a significantly elevated of DNACR was detected in osteosarcoma tissue and cell lines. Functional experiments suggested that down-regulation of DANCR inhibited cells proliferation, migration, invasion and autophagy but induced apoptosis in osteosarcoma in vitro. Additionally, we also determined knockdown of DANCR inhibited the growth and autophagy of osteosarcoma in vivo. DANCR was a sponge of miR-216a-5p activity. DANCR regulated survival of osteosarcoma through targeting miR-216a-5p. Additionally, SOX5 was a direct target of miR-216a-5p, overexpression miR-216a-5p exerted inhibition effects via down-regulating SOX5 expression. Furthermore, DANCR regulated SOX5 expression by sponging to miR-216a-5p. In conclusion, LncRNA DANCR silence inhibits SOX5-medicated progression and autophagy in osteosarcoma via regulating miR-216a-5p which indicating DANCR may act as a potential prognostic biomarker and therapeutic target for osteosarcoma.
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PMID:LncRNA DANCR silence inhibits SOX5-medicated progression and autophagy in osteosarcoma via regulating miR-216a-5p. 3191 78