RT Journal Article
SR Electronic
T1 shRNA-WT1 Potentiates Anticancer Effects of Gemcitabine and Cisplatin Against B16F10 Lung Metastases In Vitro and In Vivo
JF In Vivo
JO In Vivo
FD International Institute of Anticancer Research
SP 777
OP 785
DO 10.21873/invivo.11539
VO 33
IS 3
A1 PABLO ZAPATA-BENAVIDES
A1 FERNANDA GUADALUPE THOMPSON-ARMENDARIZ
A1 MARIELA ARELLANO-RODRÍGUEZ
A1 MOISÉS ARMIDES FRANCO-MOLINA
A1 EDGAR MENDOZA-GAMBOA
A1 SANTIAGO SAAVEDRA-ALONSO
A1 JOSÉ LUIS ZACARIAS-HERNÁNDEZ
A1 LAURA MARÍA TREJO-AVILA
A1 CRISTINA RODRÍGUEZ-PADILLA
YR 2019
UL http://iv.iiarjournals.org/content/33/3/777.abstract
AB Background/Aim: High expression level of Wilm's tumor gene (WT1) in several types of tumors appears to confer disruption of apoptosis and resistance to chemotherapeutic drugs, and correlate with poor outcome. The aim of this work was to determine if down-regulation of WT1 expression results in decreased cell proliferation and the increased action of different types of drugs, both in vitro in B16F10 cells, and in vivo in C57BL/6 mice. Materials and Methods: Inhibition of cell proliferation by short hairpin RNA against WT1 (shRNA-WT1), cisplatin, and gemcitabine in B16F10 cells in vitro was determined by the MTT assay and analysis of clonogenic survival. The apoptosis rate was determined by flow cytometry for annexin-V- fluorescein isothiocyante and propidium iodide. Results: Compared to treatment with shRNA-WT1 alone, treatment with shRNA-WT1 in combination with drugs had a synergistic inhibitory effect on B16F10 cell proliferation, particularly for the combination of cisplatin and gemcitabine at their 25% cytotoxic concentrations in vitro. Furthermore, mice treated with shRNA-WT1 in combination with cisplatin and gemcitabine were protected in the same way as those treated with the drugs alone, but were in better physical condition. Conclusion: Decreased WT1 expression induces cell death and potentiates the action of anticancer drugs by inducing synergistic effects both in vitro and in vivo, which may be an attractive strategy in lung cancer therapy.