Ganoderic Acid Restores the Sensitivity of Multidrug Resistance Cancer Cells to Doxorubicin

2013 ◽  
Vol 834-836 ◽  
pp. 573-576
Author(s):  
Jing Jing Ouyang ◽  
Yu Qiang Wang ◽  
Wen Tang

Ganoderic acid R (GA-R) possessed significant cytotoxicity on a multidrug resistance (MDR) tumor cell line (KB-A-1/Dox) and a sensitive tumor cell line (KB-A-1). The results indicated that the inhibition effect of the GA-R was due to the induction of apoptosis. The use of GA-R in vitro resulted in a restoration response of the KB-A-1/Dox cells to the anti-tumor drug doxorubicin by stimulating the drug accumulation within the cells. The index of MDR reversion of GA-R was about 22 folds. The findings show that the ganoderma triterpene may be good candidates for anti-tumor and anti MDR chemotherapy.

2022 ◽  
Vol 4 (1) ◽  
Author(s):  
Paul Prasse ◽  
Pascal Iversen ◽  
Matthias Lienhard ◽  
Kristina Thedinga ◽  
Chris Bauer ◽  
...  

ABSTRACT Computational drug sensitivity models have the potential to improve therapeutic outcomes by identifying targeted drug components that are likely to achieve the highest efficacy for a cancer cell line at hand at a therapeutic dose. State of the art drug sensitivity models use regression techniques to predict the inhibitory concentration of a drug for a tumor cell line. This regression objective is not directly aligned with either of these principal goals of drug sensitivity models: We argue that drug sensitivity modeling should be seen as a ranking problem with an optimization criterion that quantifies a drug’s inhibitory capacity for the cancer cell line at hand relative to its toxicity for healthy cells. We derive an extension to the well-established drug sensitivity regression model PaccMann that employs a ranking loss and focuses on the ratio of inhibitory concentration and therapeutic dosage range. We find that the ranking extension significantly enhances the model’s capability to identify the most effective anticancer drugs for unseen tumor cell profiles based in on in-vitro data.


1992 ◽  
Vol 13 (7) ◽  
pp. 1209-1215 ◽  
Author(s):  
Wolfram C.M. Dempke ◽  
Sharon A. Shellard ◽  
Louise K. Hosking ◽  
Anne Marie J. Fichtinger-Schepman ◽  
Bridget T. Hill

2005 ◽  
Vol 26 (5) ◽  
pp. 908-915 ◽  
Author(s):  
Isabella T. Tai ◽  
Meiru Dai ◽  
Lan Bo Chen

1991 ◽  
Vol 174 (6) ◽  
pp. 1291-1298 ◽  
Author(s):  
H Hock ◽  
M Dorsch ◽  
T Diamantstein ◽  
T Blankenstein

The potential of interleukin 7 (IL-7) to induce an antitumor response in vivo was analyzed. Therefore, the IL-7 gene was expressed in the plasmacytoma cell line J558L. Although the growth of IL-7-producing cells was not retarded in vitro, the IL-7-producing cells were completely rejected upon injection into mice. Tumor rejection was observed only in syngeneic but not in nude mice. The tumor-suppressive effect could be abolished by the parallel injection of an anti-IL-7 monoclonal antibody. Immunohistochemical analysis revealed IL-7-dependent infiltration of the tumor tissue by CD4+ and CD8+ T lymphocytes, and also type 3 complement receptor-positive (CR3+) cells, predominantly macrophages. Depletion of T cell subsets in tumor-bearing mice showed the absolute dependence of the antitumor response on CD4+ cells, whereas tumor rejection was unaffected by depletion of CD8+ cells. In addition to CD4+ cells, CR3+ cells were also needed for tumor rejection. The antitumor effect of IL-7 was confirmed by expression of the IL-7 gene in a second tumor cell line of different cellular origin. Together, our results demonstrate that a high local IL-7 concentration at the tumor site obtained by tumor cell-targeted gene transfer leads to tumor rejection involving a cellular mechanism that seems to be different from the ones observed in analogous experiments with other cytokines.


2017 ◽  
Vol 22 (5) ◽  
pp. 484-493
Author(s):  
Sonia G. Escobar ◽  
Mark H. Chin ◽  
Mark L. Sandberg ◽  
Han Xu

Despite key advances in cancer therapies, malignant tumors, such as melanoma, continue to be one of the leading causes of mortality. Recent debate on whether cancer can originate from a tumor-initiating subpopulation has permeated oncology and stem cell research. It has been well established that primary and immortalized tumor cells consist of heterogeneous cell populations. The profound effect of tumor heterogeneity on tumor growth and drug resistance remains elusive, but it is highly likely that subpopulations of cancer cells have different capabilities of self-renewal and drug resistance. Discrepancies between excellent in vitro potency and efficacy and poor patient response have been observed on multiple cancer therapeutics. Although this observation can be attributed to many factors, a better understanding of the contribution from subpopulations within a cancer will help bridge the gap between in vitro assay results and patient prognosis. To comprehend this impact, it is critical to isolate and characterize cancer subpopulations that possess higher growth and drug resistance properties so that novel therapeutics can be developed to eventually eradicate all cancer cells. In this article, we describe a method to enrich a subpopulation, CB4, from the melanoma cell line WM115. CB4 exhibited higher anchorage-independent growth, higher survival under serum starvation condition, and lower drug sensitivity to commonly used melanoma treatment compared with WM115. Details of functional properties and gene expression of CB4 compared with WM115 are reported. Our study demonstrates that it is feasible to isolate and enrich a subpopulation that exhibits higher growth capacity and treatment resistance from an immortalized tumor cell line.


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