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Overexpression of FOXM1 is associated with metastases of nasopharyngeal carcinoma.

Jiang L, Wang P, Chen H - Ups. J. Med. Sci. (2014)

Bottom Line: FOXM1 was overexpressed in NPC and C666-1 cells compared with normal nasopharyngeal tissues and NP69 cells.Moreover, thiostrepton inhibited expression of FOXM1 in C666-1 cells in a dose-dependent manner, but had a minimal effect on NP69 cells.Thiostrepton inhibits the metastatic ability of NPC cells by down-regulating the expression of FOXM1, MMP-2, MMP-9, fascin-1, and paxillin.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University , 1 Youyi Road, 400016 Chongqing , P.R. China.

ABSTRACT

Background: The forkhead box M1 (FOXM1) transcription factor plays an important role in the metastases of many cancers. Down-regulation of FOXM1 by its inhibitor, thiostrepton, can inhibit the metastatic potential of some cancers; however, there are few studies regarding the functional significance of FOXM1 and thiostrepton in the metastases of nasopharyngeal carcinoma (NPC) and the underlying mechanism.

Methods: Expression of FOXM1 in NPC, normal nasopharyngeal tissues, a NPC cell line (C666-1), and a nasopharyngeal epithelial cell line (NP69) was investigated by immunohistochemical staining, qRT-PCR, and Western blot. The correlation between FOXM1 expression and the clinical characteristics of patients was analyzed. Moreover, the effects of thiostrepton on expression of FOXM1 in C666-1 and NP69 cells, and the invasion and migration ability of C666-1 cells were examined. The expressions of MMP-2, MMP-9, fascin-1, ezrin, and paxillin were determined after treatment with thiostrepton.

Results: FOXM1 was overexpressed in NPC and C666-1 cells compared with normal nasopharyngeal tissues and NP69 cells. Overexpression of FOXM1 was associated with lymph node metastasis and advanced tumor stage. Moreover, thiostrepton inhibited expression of FOXM1 in C666-1 cells in a dose-dependent manner, but had a minimal effect on NP69 cells. Thiostrepton inhibited the migration and invasion ability of C666-1 cells by down-regulating the expression of MMP-2, MMP-9, fascin-1, and paxillin.

Conclusions: Overexpression of FOXM1 is associated with metastases of NPC patients. Thiostrepton inhibits the metastatic ability of NPC cells by down-regulating the expression of FOXM1, MMP-2, MMP-9, fascin-1, and paxillin.

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Thiostrepton significantly reduces the expression of FOXM1 mRNA and protein in a NPC cell line other than a nasopharyngeal epithelial cell line. A: The expression of FOXM1 mRNA in C666-1 cells was inhibited after thiostrepton treatment at 2, 4, or 6 µM for 48 h. B: Thiostrepton down-regulated the expression of FOXM1 protein in C666-1 cells. C: The expression of FOXM1 mRNA in NP69 cells was lower than in C666-1 cells and was less affected by thiostrepton. Experiments were independently repeated three times. *p < 0.05.
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Figure 2: Thiostrepton significantly reduces the expression of FOXM1 mRNA and protein in a NPC cell line other than a nasopharyngeal epithelial cell line. A: The expression of FOXM1 mRNA in C666-1 cells was inhibited after thiostrepton treatment at 2, 4, or 6 µM for 48 h. B: Thiostrepton down-regulated the expression of FOXM1 protein in C666-1 cells. C: The expression of FOXM1 mRNA in NP69 cells was lower than in C666-1 cells and was less affected by thiostrepton. Experiments were independently repeated three times. *p < 0.05.

Mentions: More than 90% of NPC patients in China have undifferentiated tumors; EBV is consistently present in undifferentiated NPC (22). Therefore, the EBV-positive cell line, C666-1, was more suitable for use in the current study than other EBV-negative NPC cell lines. Thiostrepton has been previously reported to inhibit the expression of FOXM1 in several cancer cell lines (18,23); however, the effects of thiostrepton on NPC and normal nasopharyngeal epithelial cell lines remain unknown. The NPC cell line, C666-1, and the transformed human nasopharyngeal epithelial cell line, NP69, were treated with 2, 4, or 6 µM thiostrepton for 48 h, and FOXM1 expression was detected by qRT-PCR and Western blot. The expression of FOXM1 mRNA in C666-1 cells was decreased in a dose-dependent manner after treatment with thiostrepton compared with the control group (Figure 2A). Similarly, the expression of FOXM1 protein in C666-1 cells was also decreased in a dose-dependent manner; notably, there was virtually no expression of FOXM1 protein after treatment with 6 µM thiostrepton (Figure 2B). However, qRT-PCR analysis suggested that FOXM1 is expressed at a lower level in NP69 cells compared with C666-1 cells, and was minimally inhibited after thiostrepton treatment (Figure 2C).


Overexpression of FOXM1 is associated with metastases of nasopharyngeal carcinoma.

Jiang L, Wang P, Chen H - Ups. J. Med. Sci. (2014)

Thiostrepton significantly reduces the expression of FOXM1 mRNA and protein in a NPC cell line other than a nasopharyngeal epithelial cell line. A: The expression of FOXM1 mRNA in C666-1 cells was inhibited after thiostrepton treatment at 2, 4, or 6 µM for 48 h. B: Thiostrepton down-regulated the expression of FOXM1 protein in C666-1 cells. C: The expression of FOXM1 mRNA in NP69 cells was lower than in C666-1 cells and was less affected by thiostrepton. Experiments were independently repeated three times. *p < 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4248072&req=5

Figure 2: Thiostrepton significantly reduces the expression of FOXM1 mRNA and protein in a NPC cell line other than a nasopharyngeal epithelial cell line. A: The expression of FOXM1 mRNA in C666-1 cells was inhibited after thiostrepton treatment at 2, 4, or 6 µM for 48 h. B: Thiostrepton down-regulated the expression of FOXM1 protein in C666-1 cells. C: The expression of FOXM1 mRNA in NP69 cells was lower than in C666-1 cells and was less affected by thiostrepton. Experiments were independently repeated three times. *p < 0.05.
Mentions: More than 90% of NPC patients in China have undifferentiated tumors; EBV is consistently present in undifferentiated NPC (22). Therefore, the EBV-positive cell line, C666-1, was more suitable for use in the current study than other EBV-negative NPC cell lines. Thiostrepton has been previously reported to inhibit the expression of FOXM1 in several cancer cell lines (18,23); however, the effects of thiostrepton on NPC and normal nasopharyngeal epithelial cell lines remain unknown. The NPC cell line, C666-1, and the transformed human nasopharyngeal epithelial cell line, NP69, were treated with 2, 4, or 6 µM thiostrepton for 48 h, and FOXM1 expression was detected by qRT-PCR and Western blot. The expression of FOXM1 mRNA in C666-1 cells was decreased in a dose-dependent manner after treatment with thiostrepton compared with the control group (Figure 2A). Similarly, the expression of FOXM1 protein in C666-1 cells was also decreased in a dose-dependent manner; notably, there was virtually no expression of FOXM1 protein after treatment with 6 µM thiostrepton (Figure 2B). However, qRT-PCR analysis suggested that FOXM1 is expressed at a lower level in NP69 cells compared with C666-1 cells, and was minimally inhibited after thiostrepton treatment (Figure 2C).

Bottom Line: FOXM1 was overexpressed in NPC and C666-1 cells compared with normal nasopharyngeal tissues and NP69 cells.Moreover, thiostrepton inhibited expression of FOXM1 in C666-1 cells in a dose-dependent manner, but had a minimal effect on NP69 cells.Thiostrepton inhibits the metastatic ability of NPC cells by down-regulating the expression of FOXM1, MMP-2, MMP-9, fascin-1, and paxillin.

View Article: PubMed Central - PubMed

Affiliation: Department of Otolaryngology, The First Affiliated Hospital of Chongqing Medical University , 1 Youyi Road, 400016 Chongqing , P.R. China.

ABSTRACT

Background: The forkhead box M1 (FOXM1) transcription factor plays an important role in the metastases of many cancers. Down-regulation of FOXM1 by its inhibitor, thiostrepton, can inhibit the metastatic potential of some cancers; however, there are few studies regarding the functional significance of FOXM1 and thiostrepton in the metastases of nasopharyngeal carcinoma (NPC) and the underlying mechanism.

Methods: Expression of FOXM1 in NPC, normal nasopharyngeal tissues, a NPC cell line (C666-1), and a nasopharyngeal epithelial cell line (NP69) was investigated by immunohistochemical staining, qRT-PCR, and Western blot. The correlation between FOXM1 expression and the clinical characteristics of patients was analyzed. Moreover, the effects of thiostrepton on expression of FOXM1 in C666-1 and NP69 cells, and the invasion and migration ability of C666-1 cells were examined. The expressions of MMP-2, MMP-9, fascin-1, ezrin, and paxillin were determined after treatment with thiostrepton.

Results: FOXM1 was overexpressed in NPC and C666-1 cells compared with normal nasopharyngeal tissues and NP69 cells. Overexpression of FOXM1 was associated with lymph node metastasis and advanced tumor stage. Moreover, thiostrepton inhibited expression of FOXM1 in C666-1 cells in a dose-dependent manner, but had a minimal effect on NP69 cells. Thiostrepton inhibited the migration and invasion ability of C666-1 cells by down-regulating the expression of MMP-2, MMP-9, fascin-1, and paxillin.

Conclusions: Overexpression of FOXM1 is associated with metastases of NPC patients. Thiostrepton inhibits the metastatic ability of NPC cells by down-regulating the expression of FOXM1, MMP-2, MMP-9, fascin-1, and paxillin.

Show MeSH
Related in: MedlinePlus