Limits...
High expression of neuroguidin increases the sensitivity of acute myeloid leukemia cells to chemotherapeutic drugs.

Chen K, Lü S, Cheng H, Tang G, Liu M, Zhou H, Wang J - J Hematol Oncol (2015)

Bottom Line: Neuroguidin (NGDN) is a eukaryotic translation initiation factor 4E binding protein.The purpose of this study was to clarify the function of NGDN and its possible mechanism of action in human myeloid leukemia cells.Furthermore, NGDN knock-down in K562/A02 cells resulted in the activation of multiple tumor-related signaling pathways, especially the mammalian target of rapamycin (mTOR) pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China. ckjzl13817210306@163.com.

ABSTRACT
Neuroguidin (NGDN) is a eukaryotic translation initiation factor 4E binding protein. The purpose of this study was to clarify the function of NGDN and its possible mechanism of action in human myeloid leukemia cells. Proliferation inhibition and apoptosis in NGDN over-expressing myeloid multidrug-resistant leukemia cells (K562/A02-NGDN) was significantly higher than in control K562/A02 cells following treatment with vincristine, etoposide, and epirubicin, indicating that NGDN over-expression can increase the sensitivity of multidrug-resistant leukemia cells to chemotherapeutic drugs. Furthermore, NGDN knock-down in K562/A02 cells resulted in the activation of multiple tumor-related signaling pathways, especially the mammalian target of rapamycin (mTOR) pathway.

No MeSH data available.


Related in: MedlinePlus

Proliferation inhibition and apoptosis in NGDN over-expressing leukemia cells (K562/A02-NGDN) after chemotherapeutic drugs treatment. The level of proliferation inhibition was examined using the CCK-8 assay following treatment with different concentrations of chemotherapeutic drugs for different lengths of time. The percentages of proliferation inhibition in K562/A02-NGDN and control K562/A02 cells after treatment with (A) vincristine (VCR), (B) etoposide (VP-16) and (C) epirubicin (EPI) are shown (mean ± SD, n = 3, star symbols: P < 0.05). The level of apoptosis was assessed using annexin V-FITC/allophycocyanin (APC ) staining by flow cytometry. The percentages of apoptosis in K562/A02-NGDN and control K562/A02 cells after treatment with (D) VCR, (E) VP-16, and (F) EPI are shown (mean ± SD, n = 3, star symbols: P < 0.05). NGDN: neuroguidin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4340276&req=5

Fig1: Proliferation inhibition and apoptosis in NGDN over-expressing leukemia cells (K562/A02-NGDN) after chemotherapeutic drugs treatment. The level of proliferation inhibition was examined using the CCK-8 assay following treatment with different concentrations of chemotherapeutic drugs for different lengths of time. The percentages of proliferation inhibition in K562/A02-NGDN and control K562/A02 cells after treatment with (A) vincristine (VCR), (B) etoposide (VP-16) and (C) epirubicin (EPI) are shown (mean ± SD, n = 3, star symbols: P < 0.05). The level of apoptosis was assessed using annexin V-FITC/allophycocyanin (APC ) staining by flow cytometry. The percentages of apoptosis in K562/A02-NGDN and control K562/A02 cells after treatment with (D) VCR, (E) VP-16, and (F) EPI are shown (mean ± SD, n = 3, star symbols: P < 0.05). NGDN: neuroguidin.

Mentions: The human myeloid multidrug-resistant leukemia cell line K562/A02 was used to generate NGDN over-expressing leukemia cells (K562/A02-NGDN) by lentiviral transduction [see Additional files 1 and 2]. The proliferation of K562/A02-NGDN cells and control K562/A02 cells were assessed using the CCK-8 assay after treatment with different concentrations of vincristine (VCR), etoposide (VP-16), and epirubicin (EPI) for different lengths of time. Proliferation inhibition in K562/A02-NGDN cells was significantly higher than in control K562/A02 cells following treatment with each drug (P < 0.05) (Figure 1A,B,C). For example, after a 50-μM EPI treatment for 36 h, percent inhibition of K562/A02 and K562/A02-NGDN cell proliferation was 45.73% ± 1.93% and 59.15% ± 2.75%, respectively (P < 0.05) (Figure 1C). These results suggest that NGDN over-expression enhances the inhibitory effect of chemotherapeutic drugs on multidrug-resistant leukemia cell proliferation. Next, cell apoptosis was assessed using flow cytometry following treatment with different concentrations of VCR, VP-16, and EPI for different lengths of time. Apoptosis in K562/A02-NGDN cells was significantly higher than in K562/A02 cells (P < 0.05) (Figure 1D,E,F). For example, after a 200-μM EPI treatment for 24 h, the percentage of apoptosis detected in K562/A02 and K562/A02-NGDN cells was 23.85% ± 1.06% and 41.9% ± 3.25%, respectively (P < 0.05) (Figure 1F). These results suggest that NGDN over-expression can also enhance the apoptosis-inducing effect of chemotherapeutic drugs on multidrug-resistant leukemia cells. The effects of NGDN over-expression were also confirmed in human myeloid leukemia line K562 [see Additional files 1 and 3].Figure 1


High expression of neuroguidin increases the sensitivity of acute myeloid leukemia cells to chemotherapeutic drugs.

Chen K, Lü S, Cheng H, Tang G, Liu M, Zhou H, Wang J - J Hematol Oncol (2015)

Proliferation inhibition and apoptosis in NGDN over-expressing leukemia cells (K562/A02-NGDN) after chemotherapeutic drugs treatment. The level of proliferation inhibition was examined using the CCK-8 assay following treatment with different concentrations of chemotherapeutic drugs for different lengths of time. The percentages of proliferation inhibition in K562/A02-NGDN and control K562/A02 cells after treatment with (A) vincristine (VCR), (B) etoposide (VP-16) and (C) epirubicin (EPI) are shown (mean ± SD, n = 3, star symbols: P < 0.05). The level of apoptosis was assessed using annexin V-FITC/allophycocyanin (APC ) staining by flow cytometry. The percentages of apoptosis in K562/A02-NGDN and control K562/A02 cells after treatment with (D) VCR, (E) VP-16, and (F) EPI are shown (mean ± SD, n = 3, star symbols: P < 0.05). NGDN: neuroguidin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4340276&req=5

Fig1: Proliferation inhibition and apoptosis in NGDN over-expressing leukemia cells (K562/A02-NGDN) after chemotherapeutic drugs treatment. The level of proliferation inhibition was examined using the CCK-8 assay following treatment with different concentrations of chemotherapeutic drugs for different lengths of time. The percentages of proliferation inhibition in K562/A02-NGDN and control K562/A02 cells after treatment with (A) vincristine (VCR), (B) etoposide (VP-16) and (C) epirubicin (EPI) are shown (mean ± SD, n = 3, star symbols: P < 0.05). The level of apoptosis was assessed using annexin V-FITC/allophycocyanin (APC ) staining by flow cytometry. The percentages of apoptosis in K562/A02-NGDN and control K562/A02 cells after treatment with (D) VCR, (E) VP-16, and (F) EPI are shown (mean ± SD, n = 3, star symbols: P < 0.05). NGDN: neuroguidin.
Mentions: The human myeloid multidrug-resistant leukemia cell line K562/A02 was used to generate NGDN over-expressing leukemia cells (K562/A02-NGDN) by lentiviral transduction [see Additional files 1 and 2]. The proliferation of K562/A02-NGDN cells and control K562/A02 cells were assessed using the CCK-8 assay after treatment with different concentrations of vincristine (VCR), etoposide (VP-16), and epirubicin (EPI) for different lengths of time. Proliferation inhibition in K562/A02-NGDN cells was significantly higher than in control K562/A02 cells following treatment with each drug (P < 0.05) (Figure 1A,B,C). For example, after a 50-μM EPI treatment for 36 h, percent inhibition of K562/A02 and K562/A02-NGDN cell proliferation was 45.73% ± 1.93% and 59.15% ± 2.75%, respectively (P < 0.05) (Figure 1C). These results suggest that NGDN over-expression enhances the inhibitory effect of chemotherapeutic drugs on multidrug-resistant leukemia cell proliferation. Next, cell apoptosis was assessed using flow cytometry following treatment with different concentrations of VCR, VP-16, and EPI for different lengths of time. Apoptosis in K562/A02-NGDN cells was significantly higher than in K562/A02 cells (P < 0.05) (Figure 1D,E,F). For example, after a 200-μM EPI treatment for 24 h, the percentage of apoptosis detected in K562/A02 and K562/A02-NGDN cells was 23.85% ± 1.06% and 41.9% ± 3.25%, respectively (P < 0.05) (Figure 1F). These results suggest that NGDN over-expression can also enhance the apoptosis-inducing effect of chemotherapeutic drugs on multidrug-resistant leukemia cells. The effects of NGDN over-expression were also confirmed in human myeloid leukemia line K562 [see Additional files 1 and 3].Figure 1

Bottom Line: Neuroguidin (NGDN) is a eukaryotic translation initiation factor 4E binding protein.The purpose of this study was to clarify the function of NGDN and its possible mechanism of action in human myeloid leukemia cells.Furthermore, NGDN knock-down in K562/A02 cells resulted in the activation of multiple tumor-related signaling pathways, especially the mammalian target of rapamycin (mTOR) pathway.

View Article: PubMed Central - PubMed

Affiliation: Department of Hematology, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai, 200433, China. ckjzl13817210306@163.com.

ABSTRACT
Neuroguidin (NGDN) is a eukaryotic translation initiation factor 4E binding protein. The purpose of this study was to clarify the function of NGDN and its possible mechanism of action in human myeloid leukemia cells. Proliferation inhibition and apoptosis in NGDN over-expressing myeloid multidrug-resistant leukemia cells (K562/A02-NGDN) was significantly higher than in control K562/A02 cells following treatment with vincristine, etoposide, and epirubicin, indicating that NGDN over-expression can increase the sensitivity of multidrug-resistant leukemia cells to chemotherapeutic drugs. Furthermore, NGDN knock-down in K562/A02 cells resulted in the activation of multiple tumor-related signaling pathways, especially the mammalian target of rapamycin (mTOR) pathway.

No MeSH data available.


Related in: MedlinePlus