Dataset Information

Simultaneous targeting therapy for lung metastasis and breast tumor by blocking the NF-?B signaling pathway using Celastrol-loaded micelles.

ABSTRACT: Metastasis is one of the major obstacles for successful therapy of breast tumor. To inhibit the metastasis and growth of breast tumor simultaneously, a Celastrol (Cela) loaded glucolipid-like conjugates (CSOSA/Cela) with ?v?3-ligand Tetraiodothyroacetic acid (TET) modification (TET-CSOSA/Cela) were established to block nuclear factor-kappa B (NF-?B) signaling pathway. The distribution of TET-CSOSA was remarkably increased in lung metastasis and primary tumor of 4T1 tumor-bearing mice by means of ?v?3 receptor-mediated interaction. The results demonstrated that TET-CSOSA/Cela significantly suppressed Bcl-2 activation of lung metastatic cells and reduced MMP-9 expression of 4T1 breast tumor cells by blocking NF-?B. The inhibitory rates of TET-CSOSA/Cela against lung metastasis and primary tumor were raised to 90.72 and 81.15%, compared to those of Celastrol (72.15 and 46.40%), respectively. All results demonstrated the ?v?3 receptor targeted TET-CSOSA/Cela micelles exhibited great potential in treating lung metastasis and primary tumor simultaneously via blocking NF-?B signaling pathway.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC6058533 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Simultaneous targeting therapy for lung metastasis and breast tumor by blocking the NF-κB signaling pathway using Celastrol-loaded micelles.

Zhao Yue Y Tan Yanan Y Meng Tingting T Liu Xuan X Zhu Yun Y Hong Yun Y Yang Xiqin X Yuan Hong H Huang Xuan X Hu Fuqiang F

Drug delivery 20181101 1

Metastasis is one of the major obstacles for successful therapy of breast tumor. To inhibit the metastasis and growth of breast tumor simultaneously, a Celastrol (Cela) loaded glucolipid-like conjugates (CSOSA/Cela) with αvβ3-ligand Tetraiodothyroacetic acid (TET) modification (TET-CSOSA/Cela) were established to block nuclear factor-kappa B (NF-κB) signaling pathway. The distribution of TET-CSOSA was remarkably increased in lung metastasis and primary tumor of 4T1 tumor-bearing mice by means of ...[more]

PMID: 29355035

Similar Datasets

Project description:Objectives: Osteoarthritis (OA) is a joint disease characterized by degeneration of joint cartilage and is a significant cause of severe joint pain, physical disability, and impaired quality of life in the aging population. Celastrol, a Chinese herbal medicine, has attracted wide interests because of its anti-inflammatory effects on a variety of diseases. This study aimed to investigate the effect of celastrol on OA as well as the mechanisms in vivo and in vitro. Methods: A rat knee OA model was established using "medial collateral ligament transection (MCLT) + partial meniscectomy (pMMT)". Eight weeks after surgery, the OA rats started to receive intra-articular injection of celastrol (1 mg/kg) once a week. Safranin O-fast green (S&F) and hematoxylin and eosin (H&E) staining were used to estimate histopathological changes. Micro-CT was used to evaluate bone volume of the subchondral bone of the knee joint. Chondrocytes were isolated from the knee cartilage of rats and OA patients. Enzyme linked immunosorbent assay (ELISA), Western Blot (WB), Polymerase Chain Reaction (PCR), and Immunohistochemistry (IHC) were used to detect the expression of inflammatory factors and stromal proteins, respectively. Results: We found that celastrol treatment significantly delayed the progression of cartilage damage with a significant reduction in osteophyte formation and bone resorption in OA rat model. In IL-1β-stimulated rat chondrocytes, celastrol significantly suppressed the production of inflammatory factors such as cyclooxygenase-2 (COX2), interleukin-6 (IL-6), and prostaglandin E2 (PEG2), and reduced IL-1β-induced matrix degradation by down-regulating the expression of matrix metalloproteinase 13 (MMP13). In addition, we found that toll-like receptor 2 (TLR2) was up-regulated in OA patients and rat knee OA models, while celastrol inhibited TLR2 signal and its downstream nuclear factor-kappa B (NF-κB) phosphorylation. Conclusion: In summary, celastrol may improve OA by inhibiting the TLR2/NF-κB signaling pathway, which provides innovative strategies for the treatment of OA.

Dataset Information

Simultaneous targeting therapy for lung metastasis and breast tumor by blocking the NF-?B signaling pathway using Celastrol-loaded micelles.

Publications

Simultaneous targeting therapy for lung metastasis and breast tumor by blocking the NF-κB signaling pathway using Celastrol-loaded micelles.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets