Small molecule inhibitor SB203580 enhances the antitumor effect of gefitinib in PC-9 and A549 lung cancer cell lines / 中华肿瘤杂志
Chinese Journal of Oncology
; (12): 103-108, 2013.
Article
en Zh
| WPRIM
| ID: wpr-284229
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WPRO
ABSTRACT
<p><b>OBJECTIVE</b>To detect the inhibitory effect of a p38MAPK inhibitor SB203580 in combination with gefitinib on lung adenocarcinoma cell line PC-9 cells and A549 cells, and its cellular and molecular mechanisms of action.</p><p><b>METHODS</b>MTT test was used to detect the growth inhibition of PC-9 and A549 cells by SB203580 alone and in combination with gefitinib. Cell apoptosis and cell cycles were determined by flow cytometry. The expressions of p38 and phosphorylated -p38 proteins in the two cell lines were analyzed by immunofluorescence microscopy. The associated protein expression was determined by Western-blot.</p><p><b>RESULTS</b>Compared with the SB203580 group and gefitinib group, the growth inhibition and cell apoptosis of PC-9 cells in the SB203580 + gefitinib group were significantly increased (P < 0.05). The inhibition rate of PC-9 cells of 2 µmol/L SB203580 + 0.01 µmol/L gefitinib group was (46.6 ± 2.4)%, significantly higher than that induced by 0.01 µmol/L gefitinib (12.7 ± 1.5%) (P < 0.05). Immunofluorescence microscopy showed a low expression of phosphorylated-p38 protein in A549 cells and high expression in PC-9 cells. Flow cytometry showed that PC-9 cells in the SB203580 + gefitinib group were (77.35 ± 2.83)% at G0/G1 phase, (3.38 ± 0.84)% at S phase, and (19.56 ± 1.99)% at G2/M phase. Western-blotting showed that compared with the control group, the expression of phosphorylated Akt and phospho-p38 proteins in PC-9 cells of the SB203580 + gefitinib group was almost completely suppressed.</p><p><b>CONCLUSIONS</b>The results indicate that the small molecular inhibitor SB203580 can effectively enhance the inhibitory effect of gefitinib on lung adenocarcinoma PC-9 cells. The enhanced inhibitory effect of SB203580 may be correlated with the blockage of p38MAPK signal transduction pathway.</p>
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Asunto principal:
Patología
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Farmacología
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Fosforilación
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Piridinas
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Quinazolinas
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Adenocarcinoma
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Transducción de Señal
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Ciclo Celular
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Apoptosis
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Línea Celular Tumoral
Límite:
Humans
Idioma:
Zh
Revista:
Chinese Journal of Oncology
Año:
2013
Tipo del documento:
Article