GRP78 upregulation-induced increase in cisplatin sensitivity of SPCA1 lung cancer cells / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 3341-3346, 2011.
Article
em En
| WPRIM
| ID: wpr-319120
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>Glucose regulated protein 78 (GRP78), an endoplasmic reticulum (ER) chaperone, plays a critical role in chemotherapy resistance in a variety of cancers. In this study, we investigated the up-regulation of GRP78 induced by A23187 and its association with the chemotherapeutical sensibility to cisplatin in human lung cancer cell line SPCA1.</p><p><b>METHODS</b>SPCA1 cells were pretreated with A23187 at different concentrations. The expression of GRP78 at the mRNA level was analyzed by RT-PCR; the expression of GRP78 at the protein level was determined by Western blotting and immunofluorescence assay. Cell survival was determined by MTT assay. Cell apoptosis was analyzed by flow cytometry.</p><p><b>RESULTS</b>The expression of GRP78 at both the mRNA and protein levels was obviously induced by A23187 in SPCA1 cells, with an elevation of GRP78 by 2.1-fold at the mRNA level and by 3.8-fold at the protein level compared to the control. There was a dose-dependent response. Survival curve analysis demonstrated that A23187 induction caused a significant reduction of survival for the cells subjected to cisplatin treatment (P < 0.05). After treatment by cisplatin, the percentage of apoptotic cells in the A23187 pretreated group increased about three fold compared with the control group ((27.53 ± 4.32)% vs. (9.25 ± 3.64)%, P < 0.05).</p><p><b>CONCLUSIONS</b>A23187 treatment was fairly effective for the induction of GRP78 in SPCA1 cells at both the mRNA and protein levels. To a certain extent, GRP78 up-regulation by A23187 was associated with the enhancement of drug sensitivity to cisplatin in human lung cancer cell line SPCA1.</p>
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Assunto principal:
Farmacologia
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Western Blotting
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Calcimicina
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Cisplatino
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Apoptose
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Reação em Cadeia da Polimerase Via Transcriptase Reversa
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Linhagem Celular Tumoral
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Citometria de Fluxo
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Genética
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Proteínas de Choque Térmico
Limite:
Humans
Idioma:
En
Revista:
Chinese Medical Journal
Ano de publicação:
2011
Tipo de documento:
Article