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MicroRNA-7 enhances cytotoxicity induced by gefitinib in non-small cell lung cancer via inhibiting the EGFR and IGF1R signalling pathways.

Zhao JG, Men WF, Tang J - Contemp Oncol (Pozn) (2015)

Bottom Line: We found that miR-7 significantly decreased the IC50 of gefitinib and inhibited cell growth.In addition, levels of Raf1, IGF1R, and PI3K and phosphorylation levels of Akt and ERK were also significantly decreased.Our results suggest that miR-7 may provide a novel therapeutic target for the treatment of NSCLCs.

View Article: PubMed Central - PubMed

Affiliation: Shengjing Hospital of China Medical University, China.

ABSTRACT
Gefitinib is a tyrosine kinase inhibitor that has been used for the treatment of non-small-cell lung carcinoma (NSCLC). The ability of miR-7 to enhance gefitinib-induced cytotoxicity in NSCLC cells was evaluated in this study. We found that miR-7 significantly decreased the IC50 of gefitinib and inhibited cell growth. G0/G1 cell cycle arrest and cell apoptosis were increased after the treatment of gefitinib coupled with miR-7 transfection. In addition, levels of Raf1, IGF1R, and PI3K and phosphorylation levels of Akt and ERK were also significantly decreased. Our results suggest that miR-7 may provide a novel therapeutic target for the treatment of NSCLCs.

No MeSH data available.


Related in: MedlinePlus

Effect of miR-7 on the sensitivity of GEFITINIB in H460 and A549 cells. After transfected with miR-7 for 24 hours, A549 cells were exposed to different concentrations of GEFITINIB (0, 2.5, 5, 12.5, and 25 μM) for 48 hours.
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Figure 0002: Effect of miR-7 on the sensitivity of GEFITINIB in H460 and A549 cells. After transfected with miR-7 for 24 hours, A549 cells were exposed to different concentrations of GEFITINIB (0, 2.5, 5, 12.5, and 25 μM) for 48 hours.

Mentions: To test whether mir-7 in combination with an anti-EGFR inhibitor results in enhanced cytotoxic effect in A549 cells, cells were transfected with either the negative control or the mir-7 mimics, and then treated with various concentrations of GEFITINIB. Growth inhibition rates for each group were measured. For all the five concentrations of GEFITINIB tested, miR-7 and GEFITINIB co-treatment resulted in enhanced inhibition of A549 cell growth as compared to the single agent treatment (Fig. 2). This enhanced inhibitory effect was most noticeable in the group where GEFITINIB was added 72 hours after transfection of miR-7 mimics. Because serum can activate growth factor pathways parallel to the EGFR pathway, thus bypassing the inhibition of EGFR, growth inhibition assays were carried out under low serum conditions (0.5%). The IC50 of GEFITINIB was calculated based on the cell viability, which showed that miR-7 elevated GEFITINIB sensitivity five fold in A549 cells treated with GEFITINIB 48 hours after transfection (p < 0.05) and six fold in cells treated with GEFITINIB 72 hours after transfection (p < 0.05) (Table 1). Cell cycle was also affected by mir-7 and/or GEFITINIB (Fig. 3). As shown in Fig. 4, miR-7 resulted in G0/G1 cell cycle arrest (Fig. 4C) and induced cell apoptosis in A549 cells (Figure 3A and B). In addition, mir-7 co-treatment with GEFITINIB resulted in more cells to be arrested in the G0/G1 phase and increased the percentage of apoptotic cells. There was no significant difference in cell apoptosis between the 48-hour and 72-hour groups.


MicroRNA-7 enhances cytotoxicity induced by gefitinib in non-small cell lung cancer via inhibiting the EGFR and IGF1R signalling pathways.

Zhao JG, Men WF, Tang J - Contemp Oncol (Pozn) (2015)

Effect of miR-7 on the sensitivity of GEFITINIB in H460 and A549 cells. After transfected with miR-7 for 24 hours, A549 cells were exposed to different concentrations of GEFITINIB (0, 2.5, 5, 12.5, and 25 μM) for 48 hours.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4631286&req=5

Figure 0002: Effect of miR-7 on the sensitivity of GEFITINIB in H460 and A549 cells. After transfected with miR-7 for 24 hours, A549 cells were exposed to different concentrations of GEFITINIB (0, 2.5, 5, 12.5, and 25 μM) for 48 hours.
Mentions: To test whether mir-7 in combination with an anti-EGFR inhibitor results in enhanced cytotoxic effect in A549 cells, cells were transfected with either the negative control or the mir-7 mimics, and then treated with various concentrations of GEFITINIB. Growth inhibition rates for each group were measured. For all the five concentrations of GEFITINIB tested, miR-7 and GEFITINIB co-treatment resulted in enhanced inhibition of A549 cell growth as compared to the single agent treatment (Fig. 2). This enhanced inhibitory effect was most noticeable in the group where GEFITINIB was added 72 hours after transfection of miR-7 mimics. Because serum can activate growth factor pathways parallel to the EGFR pathway, thus bypassing the inhibition of EGFR, growth inhibition assays were carried out under low serum conditions (0.5%). The IC50 of GEFITINIB was calculated based on the cell viability, which showed that miR-7 elevated GEFITINIB sensitivity five fold in A549 cells treated with GEFITINIB 48 hours after transfection (p < 0.05) and six fold in cells treated with GEFITINIB 72 hours after transfection (p < 0.05) (Table 1). Cell cycle was also affected by mir-7 and/or GEFITINIB (Fig. 3). As shown in Fig. 4, miR-7 resulted in G0/G1 cell cycle arrest (Fig. 4C) and induced cell apoptosis in A549 cells (Figure 3A and B). In addition, mir-7 co-treatment with GEFITINIB resulted in more cells to be arrested in the G0/G1 phase and increased the percentage of apoptotic cells. There was no significant difference in cell apoptosis between the 48-hour and 72-hour groups.

Bottom Line: We found that miR-7 significantly decreased the IC50 of gefitinib and inhibited cell growth.In addition, levels of Raf1, IGF1R, and PI3K and phosphorylation levels of Akt and ERK were also significantly decreased.Our results suggest that miR-7 may provide a novel therapeutic target for the treatment of NSCLCs.

View Article: PubMed Central - PubMed

Affiliation: Shengjing Hospital of China Medical University, China.

ABSTRACT
Gefitinib is a tyrosine kinase inhibitor that has been used for the treatment of non-small-cell lung carcinoma (NSCLC). The ability of miR-7 to enhance gefitinib-induced cytotoxicity in NSCLC cells was evaluated in this study. We found that miR-7 significantly decreased the IC50 of gefitinib and inhibited cell growth. G0/G1 cell cycle arrest and cell apoptosis were increased after the treatment of gefitinib coupled with miR-7 transfection. In addition, levels of Raf1, IGF1R, and PI3K and phosphorylation levels of Akt and ERK were also significantly decreased. Our results suggest that miR-7 may provide a novel therapeutic target for the treatment of NSCLCs.

No MeSH data available.


Related in: MedlinePlus