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[Norcantharidin potentialize the chemosensitivity of adriamycin through the NF-κB/IκBα signaling pathway].
Zhonghua Xue Ye Xue Za Zhi. 2011 Dec; 32(12):809-13.ZX

Abstract

OBJECTIVE

To explore the synergetic effect of norcantharidin (NCTD) and adriamycin (ADR) on the proliferation and apoptosis of multiple myeloma (MM) cells.

METHODS

Human MM cell line U266 cells were treated with NCTD alone (10 µmol/L) or in combination with ADR (0.25 µmol/L). MTT and Annexin V/PI staining were used to determine cell viability and apoptosis. The protein expression of nuclear factor-κB P65 (NF-κB P65), phosphorylated NF-κB p65 (p-NF-κB p65), NF-κB P65 inhibitor IκBα, phosphorylated IκBα (p-IκBα), survivin, Bcl-2 and Bax were determined by Western blot. Immunohistochemistry was used to determine the expression of vascular endothelial growth factor (VEGF).

RESULTS

(1) NCTD potentiated the cytotoxicity and pro-apoptotic effects induced by ADR. The combination of NCTD and ADR had synergistic anti-proliferation effect. (2) Combination of ADR and NCTD downregulated the expression of nuclear NF-κB P65 and cytoplasm p-IκBα induced by ADR. The expression of nuclear NF-κB P65 and cytoplasm p-IκBα decreased from 2.08 ± 0.29 and 0.39 ± 0.07 to 0.48 ± 0.08 and 0.02 ± 0.01 respectively, while the expression of the cytoplasm NF-κB P65 and IκBα were unchanged in the ADR alone group and the combined group. (3) The expression of survivin and bcl-2 decreased from 0.31 ± 0.05 and 0.23 ± 0.05 to 0.03 ± 0.02 and 0.05 ± 0.02, while the expression of Bax increased from 0.46 ± 0.06 to 0.62 ± 0.08 respectively in ADR alone group and combined group. (4) The positive rate of VEGF in ADR group and combination group were (44.6 ± 4.4)% and (27.0 ± 2.1)% respectively, indicating that NCTD could potentiate the inhibition effect on VEGF induced by ADR.

CONCLUSIONS

The results suggest that NCTD can potentialize the chemosensitivity of multiple myeloma cells to ADR through regulating NF-κB/IκBα signaling pathway and NF-κB-regulated gene products including survivin, Bcl-2, Bax and VEGF.

Links

Publisher Full Text

Authors+Show Affiliations

Song XN
Department of Hematology, Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.
Du HF
No affiliation info available
Yu LJ
No affiliation info available
Meng YF
No affiliation info available
Lü HY
No affiliation info available
Sun LX
No affiliation info available
Meng JB
No affiliation info available
Zhang JQ
No affiliation info available

MeSH

Bridged Bicyclo Compounds, HeterocyclicCell Line, TumorCell ProliferationDown-RegulationDoxorubicinHumansI-kappa B ProteinsInhibitor of Apoptosis ProteinsMultiple MyelomaNF-KappaB Inhibitor alphaProto-Oncogene Proteins c-bcl-2Signal TransductionSurvivinTranscription Factor RelAVascular Endothelial Growth Factor Abcl-2-Associated X Protein

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

chi

PubMed ID

22339951

Citation

Song, Xiao-ning, et al. "[Norcantharidin Potentialize the Chemosensitivity of Adriamycin Through the NF-κB/IκBα Signaling Pathway]." Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi, vol. 32, no. 12, 2011, pp. 809-13.
Song XN, Du HF, Yu LJ, et al. [Norcantharidin potentialize the chemosensitivity of adriamycin through the NF-κB/IκBα signaling pathway]. Zhonghua Xue Ye Xue Za Zhi. 2011;32(12):809-13.
Song, X. N., Du, H. F., Yu, L. J., Meng, Y. F., Lü, H. Y., Sun, L. X., Meng, J. B., & Zhang, J. Q. (2011). [Norcantharidin potentialize the chemosensitivity of adriamycin through the NF-κB/IκBα signaling pathway]. Zhonghua Xue Ye Xue Za Zhi = Zhonghua Xueyexue Zazhi, 32(12), 809-13.
Song XN, et al. [Norcantharidin Potentialize the Chemosensitivity of Adriamycin Through the NF-κB/IκBα Signaling Pathway]. Zhonghua Xue Ye Xue Za Zhi. 2011;32(12):809-13. PubMed PMID: 22339951.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - [Norcantharidin potentialize the chemosensitivity of adriamycin through the NF-κB/IκBα signaling pathway]. AU - Song,Xiao-ning, AU - Du,Heng-fei, AU - Yu,Lu-jia, AU - Meng,Yan-feng, AU - Lü,Hong-yan, AU - Sun,Li-xia, AU - Meng,Jian-bo, AU - Zhang,Jin-qiao, PY - 2012/2/21/entrez PY - 2012/2/22/pubmed PY - 2012/5/18/medline SP - 809 EP - 13 JF - Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi JO - Zhonghua Xue Ye Xue Za Zhi VL - 32 IS - 12 N2 - OBJECTIVE: To explore the synergetic effect of norcantharidin (NCTD) and adriamycin (ADR) on the proliferation and apoptosis of multiple myeloma (MM) cells. METHODS: Human MM cell line U266 cells were treated with NCTD alone (10 µmol/L) or in combination with ADR (0.25 µmol/L). MTT and Annexin V/PI staining were used to determine cell viability and apoptosis. The protein expression of nuclear factor-κB P65 (NF-κB P65), phosphorylated NF-κB p65 (p-NF-κB p65), NF-κB P65 inhibitor IκBα, phosphorylated IκBα (p-IκBα), survivin, Bcl-2 and Bax were determined by Western blot. Immunohistochemistry was used to determine the expression of vascular endothelial growth factor (VEGF). RESULTS: (1) NCTD potentiated the cytotoxicity and pro-apoptotic effects induced by ADR. The combination of NCTD and ADR had synergistic anti-proliferation effect. (2) Combination of ADR and NCTD downregulated the expression of nuclear NF-κB P65 and cytoplasm p-IκBα induced by ADR. The expression of nuclear NF-κB P65 and cytoplasm p-IκBα decreased from 2.08 ± 0.29 and 0.39 ± 0.07 to 0.48 ± 0.08 and 0.02 ± 0.01 respectively, while the expression of the cytoplasm NF-κB P65 and IκBα were unchanged in the ADR alone group and the combined group. (3) The expression of survivin and bcl-2 decreased from 0.31 ± 0.05 and 0.23 ± 0.05 to 0.03 ± 0.02 and 0.05 ± 0.02, while the expression of Bax increased from 0.46 ± 0.06 to 0.62 ± 0.08 respectively in ADR alone group and combined group. (4) The positive rate of VEGF in ADR group and combination group were (44.6 ± 4.4)% and (27.0 ± 2.1)% respectively, indicating that NCTD could potentiate the inhibition effect on VEGF induced by ADR. CONCLUSIONS: The results suggest that NCTD can potentialize the chemosensitivity of multiple myeloma cells to ADR through regulating NF-κB/IκBα signaling pathway and NF-κB-regulated gene products including survivin, Bcl-2, Bax and VEGF. SN - 0253-2727 UR - https://www.unboundmedicine.com/medline/citation/22339951/[Norcantharidin_potentialize_the_chemosensitivity_of_adriamycin_through_the_NF_κB/IκBα_signaling_pathway]_ L2 - http://journal.yiigle.com/LinkIn.do?linkin_type=pubmed&issn=0253-2727&year=2011&vol=32&issue=12&fpage=809 DB - PRIME DP - Unbound Medicine ER -
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