Enhanced growth inhibition by combined two pathway inhibitors on K-ras mutated non-small cell lung cancer cells / 中华肿瘤杂志
Chinese Journal of Oncology
;
(12): 645-650, 2014.
Artigo
em Chinês
| WPRIM
| ID: wpr-272317
ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of combined targeting of MEK and PI3K signaling pathways on K-ras mutated non-small cell lung cancer cell line A549 cells and the relevant mechanisms.</p><p><b>METHODS</b>A549 cells were treated with different concentrations of two inhibitors. Growth inhibition was determined by MTT assay. According to the results of MTT test, the cells were divided into four groups the control group, PI3K inhibitor group (GDC-0941,0.5 and 5.0 µmol/L), combination group I (0.5 µmol/L AZD6244+0.5 µmol/L GDC-0941) and combination group II (5.0 µmol/L AZD6244+5.0 µmol/L GDC-0941). The cell cycle and apoptosis were analyzed by flow cytometry. The expression of proteins related to apoptosis was tested with Western blot.</p><p><b>RESULTS</b>Both GDC-0941 and AZD6244 inhibited the cell proliferation. The combination group II led to a stronger growth inhibition. The combination group I showed an antagonistic effect and combination group II showed an additive or synergistic effect. Compared with the control group, the combination group I led to reduced apoptotic rate [(20.70 ± 0.99)% vs. (18.65 ± 0.92 )%, P > 0.05]; Combination group II exhibited enhanced apoptotic rate [(37.85 ± 3.18)% vs. (52.27 ± 4.36)%, P < 0.01]. In addition, in the combination group II, more A549 cells were arrested in G0/G1 phase and decreased S phase (P < 0.01), due to the reduced expressions of CyclinD1 and Cyclin B1, the increased cleaved PARP and the diminished ratio of Bcl-2/Bax.</p><p><b>CONCLUSIONS</b>For single K-ras mutated NSCLC cell line A549 cells, combination of RAS/MEK/ERK and PI3K/AKT/mTOR inhibition showed synergistic effects depending on the drug doses. Double pathways targeted therapy may be beneficial for these patients.</p>
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Benzimidazóis
/
Transdução de Sinais
/
Ciclo Celular
/
Proteínas Proto-Oncogênicas p21(ras)
/
Proteínas Proto-Oncogênicas
/
Apoptose
/
Carcinoma Pulmonar de Células não Pequenas
/
Proteínas ras
/
Fosfatidilinositol 3-Quinases
/
Linhagem Celular Tumoral
Limite:
Humanos
Idioma:
Chinês
Revista:
Chinese Journal of Oncology
Ano de publicação:
2014
Tipo de documento:
Artigo
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