Document Detail


WT1 silencing by RNAi synergizes with chemotherapeutic agents and induces chemosensitization to doxorubicin and cisplatin in B16F10 murine melanoma cells.
MedLine Citation:
PMID:  22740987     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The Wilm's tumor gene (WT1), encoding a transcription factor that modulates the expression of certain genes that are involved in proliferation and apoptosis, is overexpressed in numerous solid tumors. WT1 is important for cell proliferation and in the diagnosis of melanoma. The objectives of this study were to investigate whether WT1 silencing is capable of synergizing with chemotherapeutic agents and whether this silencing is capable of sensitizing cancer cells to doxorubicin and cisplatin in the B16F10 murine melanoma cell line. In the present study, B16F10 cells were simultaneously treated with median lethal doses (LD50s) of WT1-1 or WT1-2 small hairpin RNAs (shRNAs) and chemotherapeutic agents. A total of 24 h post-transfection, a [3-(4,5-dimethylthiazol-2yl)-2,5- diphenyl tetrazolium bromide assay] MTT assay was performed. To determine whether shRNA interference (shRNAi) is capable of sensitizing B16F10 cells to chemotherapeutic agents, cells were transfected with an LD50 of each of the recombinant plasmids, treated with varying concentrations of doxorubicin or cisplatin 24 h post-transfection, and analyzed 48 h later for inhibition of cell proliferation using the MTT assay. We observed that WT1-RNAi and the two chemotherapeutic agents acted synergistically to inhibit B16F10 cell proliferation. The greatest inhibition of cell proliferation was observed with the WT1-2/cisplatin (91%) and WT1-1/cisplatin combinations (85%). WT1 silencing using shRNAi induced the chemosensitization of cells to doxorubicin and cisplatin, with the greatest inhibition (85%) of cell proliferation being observed in the cells treated with the WT1-2/cisplatin 6 ng/µl combination. Our results provide direct evidence that WT1 gene silencing has a synergistic effect with chemotherapeutic drugs and sensitizes B16F10 melanoma cells to doxorubicin and cisplatin. This suggests that these combination strategies are potentially utilized in melanoma therapy.
Authors:
Pablo Zapata-Benavides; Edgar Manilla-Muñoz; Diana E Zamora-Avila; Santiago Saavedra-Alonso; Moisés A Franco-Molina; Laura M Trejo-Avila; Guillermo Davalos-Aranda; Cristina Rodríguez-Padilla
Related Documents :
20309957 - Effect of varying osmotic conditions on the response of bovine nucleus pulposus cells t...
9808147 - Autocrine tgfalpha expression in the regulation of initiation of human colon carcinoma ...
12412767 - Feedback suppression of b cell colony formation in healthy individuals.
2404747 - Thyrotropin potentiation of insulin-like growth factor-i dependent deoxribonucleic acid...
12153987 - Directional control of lamellipodia extension by constraining cell shape and orienting ...
4530317 - Isolation of a major cell surface glycoprotein from fibroblasts.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-19
Journal Detail:
Title:  Oncology letters     Volume:  3     ISSN:  1792-1082     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-6-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101531236     Medline TA:  Oncol Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  751-755     Citation Subset:  -    
Affiliation:
Laboratorio de Inmunología y Virología, Departamento de Microbiología e Inmunología, Facultad de Ciencias Biológicas de la Universidad Autónoma de Nuevo León, San Nicolás de los Garza, N.L. México.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Epithelial cell culture models for the prevention and therapy of clinical breast cancer (Review).
Next Document:  Adiponectin receptor 2 is negatively associated with lymph node metastasis of colorectal cancer.