Combining GRP78 suppression and MK2206-induced Akt inhibition decreases doxorubicin-induced P-glycoprotein expression and mitigates chemoresistance in human osteosarcoma.
In this study, we analyzed the subcellular localization of P-glycoprotein, in a series of U-2 OS osteosarcoma cell clones transfected with MDR1 gene in order to verify whether the nucleus is a constant site for the localization and functional activity of P-glycoprotein, and in which way some aspects of cell morphology related to MDR depend on the subcellular P-glycoprotein localization rather than on the exposure to the selective drug.
The present evidence indicated that there was no association between p-glycoprotein expression and chemotherapy response in patients with osteosarcoma.
In this study we explored the correlation between (99m)Tc-MIBI clearance and histological necrosis following induction chemotherapy and P-glycoprotein expression in osteosarcoma.
Nuclear expression of the Y-box-binding protein (YB-1) has been reported to correlate with the expression of P-glycoprotein in breast cancer and osteosarcoma.
A lncRNA-mRNA co-expression network identified lncRNAs, including ENST00000563280 and NR-036444, may play a critical role in doxorubicin-resistance of OS by interacting with important genes such as ABCB1, HIF1A and FOXC2.
Then we adopted the CRISPR-Cas9, a robust and highly efficient novel genome editing tool, to determine its effect on reversing drug resistance by targeting endogenous ABCB1 gene at the DNA level in osteosarcoma MDR cell lines.
Overall, results indicate the vital role of LUCAT1 in the methotrexate resistance regulation through miR-200c/ABCB1 pathway, providing a novel insight and treatment strategy for osteosarcoma drug resistance.
In this study the U2OS human osteosarcoma cell line and its multidrug resistant (MDR) subline that overexpresses MDR-1 gene, MDR-U2OS, have been analyzed for their responsiveness to TRAIL.
Expression profiling of osteosarcoma cells transfected with MDR1 and NEO genes: regulation of cell adhesion, apoptosis, and tumor suppression-related genes.
The goal of this study was to establish human FK228-resistant osteosarcoma cell lines and to investigate whether there are mechanisms of FK228 resistance in addition to P-gp up-regulation.
In a retrospective study, we correlated P-glycoprotein expression with the outcome of conventional chemotherapy in 62 consecutive, clinically staged patients diagnosed as having osteosarcoma between 1980 and 1989.
siRNA down-regulated MDR1 mRNA expression by 50% in breast carcinoma and osteosarcoma cell lines, and significantly inhibited tumor cell proliferation up to 90% (p<0.01), when co-administered with doxorubicin or methotrexate, despite the known chemoresistance of the cell lines. siRNAs reduced the IC₅₀ of doxorubicin and methotrexate by more than 10-fold (p<0.01).
HA-Lsdox showed favorable drug-release profile and higher toxicity in vitro and in vivo than dox or the FDA-approved liposomal dox Caelyx<sup>®</sup> against Pgp-overexpressing osteosarcoma, displaying the same cardiotoxicity profile of Caelyx<sup>®</sup>.
Only increased expression of P-glycoprotein in tumor cells was significantly associated with a poor outcome, further supporting the adverse prognostic value of this marker in osteosarcoma.
These data indicate that, in osteosarcoma, the MDR phenotype is not associated with a more aggressive behavior both in vitro and in clinical settings, suggesting that the previously shown association of the MDR phenotype with a worse outcome in osteosarcoma is not related to a higher metastatic ability of cells with P-glycoprotein overexpression but is more likely due to their lack of responsiveness to cytotoxic drugs.