Downregulation of circITCH promotes osteosarcoma development and resistance to doxorubicin via the miR‐524/RASSF6 axis

2021 ◽  
Author(s):  
Wei Zhou ◽  
Yuan Liu ◽  
Xuejian Wu
Keyword(s):  
Resistance To Doxorubicin

Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death

2019 ◽  
Vol 18 (10) ◽  
pp. 1448-1456 ◽  
Author(s):  
Bahareh Movafegh ◽  
Razieh Jalal ◽  
Zobeideh Mohammadi ◽  
Seyyede A. Aldaghi
Keyword(s):  
Cell Death ◽  
Cellular Uptake ◽  
Combined Treatment ◽  
Annexin V ◽  
Cell Penetrating Peptides ◽  
Short Exposure ◽  
Dependent Manner ◽  
Du145 Cells ◽  
Induced Apoptosis ◽  
Resistance To Doxorubicin

Objective: Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell-penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. Methods: The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay. The influence of poly-L-arginine on doxorubicin delivery into cells was evaluated by fluorescence microscopy and ultraviolet spectroscopy. DAPI and ethidium bromide- acridine orange stainings, flow cytometry using annexin V/propidium iodide, western blot analysis with anti-p21 antibody and caspase-3 activity were used to examine the influence of poly-L-arginine on doxorubicininduced cell death. Results: Poly-L-arginine had no cytotoxicity at low concentrations and short exposure times. Poly-L-arginine increased the cytotoxic effect of doxorubicin in DU145 cells in a time-dependent manner. But no significant reduction was found in HFF cell viability. Poly-L-arginine seems to facilitate doxorubicin uptake and increase its intracellular concentration. 24h combined treatment of cells with doxorubicin (0.5 µM) and poly-L-arginine (1 µg ml-1) caused a small increase in doxorubicin-induced apoptosis and significantly elevated necrosis in DU145 cells as compared to each agent alone. Conclusion: Our results indicate that poly-L-arginine at lowest and highest concentrations act as proliferationinducing and antiproliferative agents, respectively. Between these concentrations, poly-L-arginine increases the cellular uptake of doxorubicin and its cytotoxicity through induction of necrosis.

scholarly journals RNA Aptamer-targeted Inhibition of NF-κB Suppresses Non-small Cell Lung Cancer Resistance to Doxorubicin

2008 ◽  
Vol 16 (1) ◽  
pp. 66-73 ◽  
Author(s):  
Jing Mi ◽  
Xiuwu Zhang ◽  
Zahid N Rabbani ◽  
Yingmiao Liu ◽  
Srinevas K Reddy ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Rna Aptamer ◽  
Cancer Resistance ◽  
Small Cell Lung ◽  
Targeted Inhibition ◽  
Resistance To Doxorubicin

Immunoexpression of Multidrug-Resistance Protein 2 and Cyclooxygenase 2 in Medullary Thyroid Carcinomas

2006 ◽  
Vol 130 (7) ◽  
pp. 1014-1019
Author(s):  
Rosaria Maddalena Ruggeri ◽  
Salvatore Sciacchitano ◽  
Enrica Vitarelli ◽  
Francesco Trimarchi ◽  
Gaetano Barresi ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cyclooxygenase 2 ◽  
Multidrug Resistance Proteins ◽  
Primary Tumors ◽  
Medullary Thyroid ◽  
Thyroid Carcinomas ◽  
Ptnm Stage ◽  
Resistance To Doxorubicin ◽  
Cox2 Expression ◽  
Medullary Thyroid Carcinomas

Abstract Context.—Chemoresistance is due to the expression of multidrug-resistance proteins (MRPs). Cyclooxygenase 2 (COX2), a key enzyme in prostaglandins synthesis, upregulates MRP1. MRP1 is overexpressed in medullary thyroid carcinomas (MTCs), but it is not involved in resistance to doxorubicin and cisplatin, which are commonly used in MTC treatment. MRP2 is specifically involved in resistance to both chemotherapeutic agents, but no data exist on the expression of MRP2 and COX2 in MTC. Objective.—To evaluate MRP2 and COX2 expressions in MTC. Design.—We analyzed immunohistochemical expression of MRP2 and COX2 in 12 MTCs and in 6 lymph node metastases. Results were correlated with pTNM and clinical stage. Results.—MRP2 and COX2 expressions were observed only in tumor samples and metastases. Nine MTCs, all pTNM stage T4, were positive for MRP2, whereas 3 MTCs, pTNM stages T2 and T3, were unreactive for MRP2. Six metastatic MTCs at stage T4 showed higher proportion of MRP2+ cells, compared with primary tumors. All 12 MTCs were positive for COX2. Three MTCs, pTNM stage T2 and T3, showed COX2 positivity in all cells. The proportion of COX2+ cells decreased with increased pTNM stage. Four out of 6 metastatic MTCs, stage T4, showed a lower proportion of COX2+ cells, compared with primary tumors. The proportion of MRP2+ cells was inversely related to the proportion of COX2+ cells. Conclusions.—MRP2 and COX2 expression correlated with pTNM stage. High MRP2 and low COX2 expression may explain resistance to doxorubicin and cisplatin, which is observed in advanced stage MTC. Evaluation of the expression pattern of these 2 proteins may be useful to predict chemosensitivity of these types of tumors.

scholarly journals The spectraplakin Dystonin antagonizes YAP activity and suppresses tumourigenesis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Praachi B. Jain ◽  
Patrícia S. Guerreiro ◽  
Sara Canato ◽  
Florence Janody
Keyword(s):  
Breast Cancer ◽  
Breast Tumour ◽  
Tissue Growth ◽  
Tumour Suppressor ◽  
Aberrant Expression ◽  
Breast Epithelial Cells ◽  
Mcf10a Cells ◽  
Resistance To Doxorubicin ◽  
Candidate Tumour Suppressor

AbstractAberrant expression of the Spectraplakin Dystonin (DST) has been observed in various cancers, including those of the breast. However, little is known about its role in carcinogenesis. In this report, we demonstrate that Dystonin is a candidate tumour suppressor in breast cancer and provide an underlying molecular mechanism. We show that in MCF10A cells, Dystonin is necessary to restrain cell growth, anchorage-independent growth, self-renewal properties and resistance to doxorubicin. Strikingly, while Dystonin maintains focal adhesion integrity, promotes cell spreading and cell-substratum adhesion, it prevents Zyxin accumulation, stabilizes LATS and restricts YAP activation. Moreover, treating DST-depleted MCF10A cells with the YAP inhibitor Verteporfin prevents their growth. In vivo, the Drosophila Dystonin Short stop also restricts tissue growth by limiting Yorkie activity. As the two Dystonin isoforms BPAG1eA and BPAG1e are necessary to inhibit the acquisition of transformed features and are both downregulated in breast tumour samples and in MCF10A cells with conditional induction of the Src proto-oncogene, they could function as the predominant Dystonin tumour suppressor variants in breast epithelial cells. Thus, their loss could deem as promising prognostic biomarkers for breast cancer.

Abstract 781: The effect of vorinostat on the development of resistance to doxorubicin in neuroblastoma

2012 ◽  
Author(s):  
Timothy B. Lautz ◽  
Chunfa Jie ◽  
Sandra Clark ◽  
Jessica A Naiditch ◽  
Nadereh Jafari ◽  
...  
Keyword(s):  
Development Of Resistance ◽  
Resistance To Doxorubicin
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