Limits...
Resveratrol Inhibits the Invasion of Glioblastoma-Initiating Cells via Down-Regulation of the PI3K/Akt/NF-κB Signaling Pathway.

Jiao Y, Li H, Liu Y, Guo A, Xu X, Qu X, Wang S, Zhao J, Li Y, Cao Y - Nutrients (2015)

Bottom Line: Resveratrol (RES) is a natural compound that exhibits anti-invasion properties in multiple tumor cell lines.Invasive behaviors, including the adhesion, invasion and migration of GICs, were determined by tumor invasive assays in vitro and in vivo.The activity of matrix metalloproteinases (MMPs) was measured by the gelatin zymography assay.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. shengxiongyuming@163.com.

ABSTRACT
Invasion and metastasis of glioblastoma-initiating cells (GICs) are thought to be responsible for the progression and recurrence of glioblastoma multiforme (GBM). A safe drug that can be applied during the rest period of temozolomide (TMZ) maintenance cycles would greatly improve the prognosis of GBM patients by inhibiting GIC invasion. Resveratrol (RES) is a natural compound that exhibits anti-invasion properties in multiple tumor cell lines. The current study aimed to evaluate whether RES can inhibit GIC invasion in vitro and in vivo. GICs were identified using CD133 and Nestin immunofluorescence staining and tumorigenesis in non-obese diabetic severe combined immunodeficient (NOD/SCID) mice. Invasive behaviors, including the adhesion, invasion and migration of GICs, were determined by tumor invasive assays in vitro and in vivo. The activity of matrix metalloproteinases (MMPs) was measured by the gelatin zymography assay. Western blotting analysis and immunofluorescence staining were used to determine the expression of signaling effectors in GICs. We demonstrated that RES suppressed the adhesion, invasion and migration of GICs in vitro and in vivo. Moreover, we proved that RES inhibited the invasion of GICs via the inhibition of PI3K/Akt/NF-κB signal transduction and the subsequent suppression of MMP-2 expression.

No MeSH data available.


Related in: MedlinePlus

Determination of GICs (412) in vitro and in vivo. (A) Suspended cells formed the self-renewing spheres in stem cell conditioned culture medium (100×); (B) Immunofluorescent staining of single suspended cells showed CD133-positive staining (200×); (C) Immunofluorescent staining of single suspended cells showed Nestin-positive staining (200×); (D) Immunofluorescent staining of DAPI (200×); (E) Morphology of serum-induced differentiation of GICs under a microscope (100×); (F) Immunofluorescent staining in differentiated GICs showed GFAP-positive staining (200×); (G) Immunofluorescent staining in differentiated GICs showed NF-positive staining (200×); (H) Immunofluorescent staining in differentiated GICs showed CNP-positive staining (200×); (I) The representative image of GIC tumorigenesis in NOD/SCID mice; the tumor is indicated by the blue arrow; (J) H & E staining showed the brain xenograft as GBM (200×); (K) Immunohistochemical staining in the xenograft section presented high expression levels of Nestin (200×); (L) Immunohistochemical staining of xenograft samples presented acicular expression of GFAP (200×).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4488790&req=5

nutrients-07-04383-f001: Determination of GICs (412) in vitro and in vivo. (A) Suspended cells formed the self-renewing spheres in stem cell conditioned culture medium (100×); (B) Immunofluorescent staining of single suspended cells showed CD133-positive staining (200×); (C) Immunofluorescent staining of single suspended cells showed Nestin-positive staining (200×); (D) Immunofluorescent staining of DAPI (200×); (E) Morphology of serum-induced differentiation of GICs under a microscope (100×); (F) Immunofluorescent staining in differentiated GICs showed GFAP-positive staining (200×); (G) Immunofluorescent staining in differentiated GICs showed NF-positive staining (200×); (H) Immunofluorescent staining in differentiated GICs showed CNP-positive staining (200×); (I) The representative image of GIC tumorigenesis in NOD/SCID mice; the tumor is indicated by the blue arrow; (J) H & E staining showed the brain xenograft as GBM (200×); (K) Immunohistochemical staining in the xenograft section presented high expression levels of Nestin (200×); (L) Immunohistochemical staining of xenograft samples presented acicular expression of GFAP (200×).

Mentions: We sorted CD133+ tumor cells from three different surgical specimens of different patients. As shown in Figure 1A–D, Immunofluorescent staining of 412 revealed the presence of stem-cell-related stemness markers such as CD133 and Nestin. Furthermore, as shown in Figure 1E–H, CD133+ cells also exhibited multilineage differentiation potential, demonstrated by high expression levels of GFAP (astrocytes)-, NF (neuron)-, and CNP (oligodendrocytes)-directed morphology in accordance of differentiation. The characteristics of GICs were also confirmed by the assay of tumorigenesis in NOD/SCID mice. As shown in Figure 1I, GICs have the distinguished character of tumorigenesis. The brain tumors were determined through H & E staining (Figure 1J). The brain samples also presented high expression levels of Nestin (Figure 1K) and acicular expression of GFAP (Figure 1L). The other two cell lines showed similar characteristics.


Resveratrol Inhibits the Invasion of Glioblastoma-Initiating Cells via Down-Regulation of the PI3K/Akt/NF-κB Signaling Pathway.

Jiao Y, Li H, Liu Y, Guo A, Xu X, Qu X, Wang S, Zhao J, Li Y, Cao Y - Nutrients (2015)

Determination of GICs (412) in vitro and in vivo. (A) Suspended cells formed the self-renewing spheres in stem cell conditioned culture medium (100×); (B) Immunofluorescent staining of single suspended cells showed CD133-positive staining (200×); (C) Immunofluorescent staining of single suspended cells showed Nestin-positive staining (200×); (D) Immunofluorescent staining of DAPI (200×); (E) Morphology of serum-induced differentiation of GICs under a microscope (100×); (F) Immunofluorescent staining in differentiated GICs showed GFAP-positive staining (200×); (G) Immunofluorescent staining in differentiated GICs showed NF-positive staining (200×); (H) Immunofluorescent staining in differentiated GICs showed CNP-positive staining (200×); (I) The representative image of GIC tumorigenesis in NOD/SCID mice; the tumor is indicated by the blue arrow; (J) H & E staining showed the brain xenograft as GBM (200×); (K) Immunohistochemical staining in the xenograft section presented high expression levels of Nestin (200×); (L) Immunohistochemical staining of xenograft samples presented acicular expression of GFAP (200×).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488790&req=5

nutrients-07-04383-f001: Determination of GICs (412) in vitro and in vivo. (A) Suspended cells formed the self-renewing spheres in stem cell conditioned culture medium (100×); (B) Immunofluorescent staining of single suspended cells showed CD133-positive staining (200×); (C) Immunofluorescent staining of single suspended cells showed Nestin-positive staining (200×); (D) Immunofluorescent staining of DAPI (200×); (E) Morphology of serum-induced differentiation of GICs under a microscope (100×); (F) Immunofluorescent staining in differentiated GICs showed GFAP-positive staining (200×); (G) Immunofluorescent staining in differentiated GICs showed NF-positive staining (200×); (H) Immunofluorescent staining in differentiated GICs showed CNP-positive staining (200×); (I) The representative image of GIC tumorigenesis in NOD/SCID mice; the tumor is indicated by the blue arrow; (J) H & E staining showed the brain xenograft as GBM (200×); (K) Immunohistochemical staining in the xenograft section presented high expression levels of Nestin (200×); (L) Immunohistochemical staining of xenograft samples presented acicular expression of GFAP (200×).
Mentions: We sorted CD133+ tumor cells from three different surgical specimens of different patients. As shown in Figure 1A–D, Immunofluorescent staining of 412 revealed the presence of stem-cell-related stemness markers such as CD133 and Nestin. Furthermore, as shown in Figure 1E–H, CD133+ cells also exhibited multilineage differentiation potential, demonstrated by high expression levels of GFAP (astrocytes)-, NF (neuron)-, and CNP (oligodendrocytes)-directed morphology in accordance of differentiation. The characteristics of GICs were also confirmed by the assay of tumorigenesis in NOD/SCID mice. As shown in Figure 1I, GICs have the distinguished character of tumorigenesis. The brain tumors were determined through H & E staining (Figure 1J). The brain samples also presented high expression levels of Nestin (Figure 1K) and acicular expression of GFAP (Figure 1L). The other two cell lines showed similar characteristics.

Bottom Line: Resveratrol (RES) is a natural compound that exhibits anti-invasion properties in multiple tumor cell lines.Invasive behaviors, including the adhesion, invasion and migration of GICs, were determined by tumor invasive assays in vitro and in vivo.The activity of matrix metalloproteinases (MMPs) was measured by the gelatin zymography assay.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China. shengxiongyuming@163.com.

ABSTRACT
Invasion and metastasis of glioblastoma-initiating cells (GICs) are thought to be responsible for the progression and recurrence of glioblastoma multiforme (GBM). A safe drug that can be applied during the rest period of temozolomide (TMZ) maintenance cycles would greatly improve the prognosis of GBM patients by inhibiting GIC invasion. Resveratrol (RES) is a natural compound that exhibits anti-invasion properties in multiple tumor cell lines. The current study aimed to evaluate whether RES can inhibit GIC invasion in vitro and in vivo. GICs were identified using CD133 and Nestin immunofluorescence staining and tumorigenesis in non-obese diabetic severe combined immunodeficient (NOD/SCID) mice. Invasive behaviors, including the adhesion, invasion and migration of GICs, were determined by tumor invasive assays in vitro and in vivo. The activity of matrix metalloproteinases (MMPs) was measured by the gelatin zymography assay. Western blotting analysis and immunofluorescence staining were used to determine the expression of signaling effectors in GICs. We demonstrated that RES suppressed the adhesion, invasion and migration of GICs in vitro and in vivo. Moreover, we proved that RES inhibited the invasion of GICs via the inhibition of PI3K/Akt/NF-κB signal transduction and the subsequent suppression of MMP-2 expression.

No MeSH data available.


Related in: MedlinePlus