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Specific Inhibition of β-Catenin in Jeko-1 Mantle Cell Lymphoma Cell Line Decreases Proliferation and Induces Apoptosis.

He J, Huang Y, Weng J, Xiao L, Weng K, Ma X - Med. Sci. Monit. (2015)

Bottom Line: In vitro studies indicated that β-catenin knockdown significantly inhibited cell proliferation and induced apoptosis in Jeko-1 cells.Both inhibitory agents increased Bax and caspase 3 proteins, and decreased Bcl-2, c-Myc, and Cyclin D1 proteins.The specific inhibition of β-catenin induces apoptosis and growth arrest, making it a potential therapeutic target against MCL.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Zhangzhou Hospital Affiliated to Fujian Medical University, Zhangzhou, Fujian, China (mainland).

ABSTRACT

Background: The canonical Wnt signaling pathway has been considered as a potent oncogenic signaling in the initiation and progression of hematological malignancies. As a key regulator of the Wnt signaling pathway, the role of β-catenin in mantle cell lymphoma (MCL) pathogenesis and progression was investigated in this study.

Material and methods: A total of 30 MCL samples were collected from patients and were examined for the expression of β-catenin and p-GSK3β using immunohistochemical (IHC) staining. Further in vitro studies employed MTT and Western blot assays detecting proliferation and apoptosis-related proteins in MCL cell line Jeko-1, which were transfected with β-catenin shRNA or specific inhibitor XAV939.

Results: Expression of β-catenin and phosphorylated glycogen synthase kinase-3 beta (p-GSK3β) in MCL was significantly higher than those in controlled samples. In vitro studies indicated that β-catenin knockdown significantly inhibited cell proliferation and induced apoptosis in Jeko-1 cells. Furthermore, XAV939 induced apoptosis and growth arrest in Jeko-1 cells. Both inhibitory agents increased Bax and caspase 3 proteins, and decreased Bcl-2, c-Myc, and Cyclin D1 proteins.

Conclusions: The specific inhibition of β-catenin induces apoptosis and growth arrest, making it a potential therapeutic target against MCL.

No MeSH data available.


Related in: MedlinePlus

β-catenin regulates proliferation and apoptosis in Jeko-1 cells. (A) Jeko-1 cells transfected with non-targeting (NT) shRNA or β-catenin shRNA were tested for β-catenin mRNA levels using RT-PCR. β-catenin mRNA was significantly suppressed by β-catenin shRNA (rightmost lane); (B) Western blotting analysis indicated that β-catenin protein was largely eliminated by β-catenin shRNA transfection; (C) MTT assays showed that β-catenin knockdown reduced the viability of Jeko-1 cells. (P<0.01 by two-way ANOVA; n=3); (D) Quantification of apoptotic cell percentage by flow cytometry. β-catenin knockdown cells were composed of a larger subset of apoptotic cells compared to the control cells. (P<0.01 by t test; n=3). Data presented as mean ±SD.
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f2-medscimonit-21-2218: β-catenin regulates proliferation and apoptosis in Jeko-1 cells. (A) Jeko-1 cells transfected with non-targeting (NT) shRNA or β-catenin shRNA were tested for β-catenin mRNA levels using RT-PCR. β-catenin mRNA was significantly suppressed by β-catenin shRNA (rightmost lane); (B) Western blotting analysis indicated that β-catenin protein was largely eliminated by β-catenin shRNA transfection; (C) MTT assays showed that β-catenin knockdown reduced the viability of Jeko-1 cells. (P<0.01 by two-way ANOVA; n=3); (D) Quantification of apoptotic cell percentage by flow cytometry. β-catenin knockdown cells were composed of a larger subset of apoptotic cells compared to the control cells. (P<0.01 by t test; n=3). Data presented as mean ±SD.

Mentions: To further elucidate the role of β-catenin in MCL, we transfected Jeko-1 cells with non-targeting (NT) shRNA or β-catenin shRNA. As measured by RT-PCR and Western blot, β-catenin mRNA and protein levels were significantly suppressed by ectopically expressing β-catenin shRNA (P<0.05, Figure 2A, 2B, respectively). MTT assays were performed to test the effect on tumor cell proliferation. Results showed that β-catenin knockdown led to a significant reduction of cell proliferation (P<0.05, Figure 2C). Furthermore, as determined by flow cytometry, the apoptosis level was significantly elevated after β-catenin knockdown (P<0.05, Figure 2D). Moreover, β-catenin knockdown increased Bax and caspase 3 protein expression and decreased Bcl-2, c-Myc, and Cyclin D1 in Jeko-1 cells (Figure 3).


Specific Inhibition of β-Catenin in Jeko-1 Mantle Cell Lymphoma Cell Line Decreases Proliferation and Induces Apoptosis.

He J, Huang Y, Weng J, Xiao L, Weng K, Ma X - Med. Sci. Monit. (2015)

β-catenin regulates proliferation and apoptosis in Jeko-1 cells. (A) Jeko-1 cells transfected with non-targeting (NT) shRNA or β-catenin shRNA were tested for β-catenin mRNA levels using RT-PCR. β-catenin mRNA was significantly suppressed by β-catenin shRNA (rightmost lane); (B) Western blotting analysis indicated that β-catenin protein was largely eliminated by β-catenin shRNA transfection; (C) MTT assays showed that β-catenin knockdown reduced the viability of Jeko-1 cells. (P<0.01 by two-way ANOVA; n=3); (D) Quantification of apoptotic cell percentage by flow cytometry. β-catenin knockdown cells were composed of a larger subset of apoptotic cells compared to the control cells. (P<0.01 by t test; n=3). Data presented as mean ±SD.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4554364&req=5

f2-medscimonit-21-2218: β-catenin regulates proliferation and apoptosis in Jeko-1 cells. (A) Jeko-1 cells transfected with non-targeting (NT) shRNA or β-catenin shRNA were tested for β-catenin mRNA levels using RT-PCR. β-catenin mRNA was significantly suppressed by β-catenin shRNA (rightmost lane); (B) Western blotting analysis indicated that β-catenin protein was largely eliminated by β-catenin shRNA transfection; (C) MTT assays showed that β-catenin knockdown reduced the viability of Jeko-1 cells. (P<0.01 by two-way ANOVA; n=3); (D) Quantification of apoptotic cell percentage by flow cytometry. β-catenin knockdown cells were composed of a larger subset of apoptotic cells compared to the control cells. (P<0.01 by t test; n=3). Data presented as mean ±SD.
Mentions: To further elucidate the role of β-catenin in MCL, we transfected Jeko-1 cells with non-targeting (NT) shRNA or β-catenin shRNA. As measured by RT-PCR and Western blot, β-catenin mRNA and protein levels were significantly suppressed by ectopically expressing β-catenin shRNA (P<0.05, Figure 2A, 2B, respectively). MTT assays were performed to test the effect on tumor cell proliferation. Results showed that β-catenin knockdown led to a significant reduction of cell proliferation (P<0.05, Figure 2C). Furthermore, as determined by flow cytometry, the apoptosis level was significantly elevated after β-catenin knockdown (P<0.05, Figure 2D). Moreover, β-catenin knockdown increased Bax and caspase 3 protein expression and decreased Bcl-2, c-Myc, and Cyclin D1 in Jeko-1 cells (Figure 3).

Bottom Line: In vitro studies indicated that β-catenin knockdown significantly inhibited cell proliferation and induced apoptosis in Jeko-1 cells.Both inhibitory agents increased Bax and caspase 3 proteins, and decreased Bcl-2, c-Myc, and Cyclin D1 proteins.The specific inhibition of β-catenin induces apoptosis and growth arrest, making it a potential therapeutic target against MCL.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Zhangzhou Hospital Affiliated to Fujian Medical University, Zhangzhou, Fujian, China (mainland).

ABSTRACT

Background: The canonical Wnt signaling pathway has been considered as a potent oncogenic signaling in the initiation and progression of hematological malignancies. As a key regulator of the Wnt signaling pathway, the role of β-catenin in mantle cell lymphoma (MCL) pathogenesis and progression was investigated in this study.

Material and methods: A total of 30 MCL samples were collected from patients and were examined for the expression of β-catenin and p-GSK3β using immunohistochemical (IHC) staining. Further in vitro studies employed MTT and Western blot assays detecting proliferation and apoptosis-related proteins in MCL cell line Jeko-1, which were transfected with β-catenin shRNA or specific inhibitor XAV939.

Results: Expression of β-catenin and phosphorylated glycogen synthase kinase-3 beta (p-GSK3β) in MCL was significantly higher than those in controlled samples. In vitro studies indicated that β-catenin knockdown significantly inhibited cell proliferation and induced apoptosis in Jeko-1 cells. Furthermore, XAV939 induced apoptosis and growth arrest in Jeko-1 cells. Both inhibitory agents increased Bax and caspase 3 proteins, and decreased Bcl-2, c-Myc, and Cyclin D1 proteins.

Conclusions: The specific inhibition of β-catenin induces apoptosis and growth arrest, making it a potential therapeutic target against MCL.

No MeSH data available.


Related in: MedlinePlus