Suppressive effects of simvastatin on the human acute promyelocytic leukemia NB4 cell line through the regulation of the nuclear factor‑κB signaling pathway

Qiu,Guoqiang; Xie,Xiaobao; Wang,Zhilin; Zeng,Mei; Jiang,Tingxiu; Zou,Zhilan; Dai,Li; Hua,Xiaoying; Gu,Weiying

doi:10.3892/ol.2014.2204

Suppressive effects of simvastatin on the human acute promyelocytic leukemia NB4 cell line through the regulation of the nuclear factor‑κB signaling pathway

Authors:
- Guoqiang Qiu
- Xiaobao Xie
- Zhilin Wang
- Mei Zeng
- Tingxiu Jiang
- Zhilan Zou
- Li Dai
- Xiaoying Hua
- Weiying Gu
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Affiliations: Laboratory of Hematology, The First People's Hospital of Changzhou, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu 213003, P.R. China, Department of Hematology, The First People's Hospital of Changzhou, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu 213003, P.R. China, Laboratory of Hematology, The First People's Hospital of Changzhou, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu 213003, P.R. China, Department of Hematology, The First People's Hospital of Kunshan, Kunshan, Jiangsu 215300, P.R. China, Department of Hematology, Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, Guangxi 545005, P.R. China, Department of Hematology, The First People's Hospital of Changzhou, Third Affiliated Hospital of Suzhou University, Changzhou, Jiangsu 213003, P.R. China
Published online on: May 30, 2014 https://doi.org/10.3892/ol.2014.2204
Pages: 693-698

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Abstract

The present study examined the effects of simvastatin on the proliferation, apoptosis and gene expression levels involved in the nuclear factor‑κB (NF‑κB) signaling pathway in the human acute promyelocytic leukemia NB4 cell line by methyl thiazolyl tetrazolium assay, flow cytometry and the Human NF‑κB Signaling Pathway RT² Profiler™ PCR Array profiles. The results showed that simvastatin significantly inhibited proliferation and induced apoptosis of the NB4 cells in a time‑ and dose‑dependent manner. Changes were noted in the expression levels of 56 genes involved in the NF‑κB signaling pathways in the NB4 cells treated with 15 µm simvastatin at 48 h post‑incubation, among which, 47 genes were downregulated and 9 were upregulated. In conclusion, simvastatin potentially inhibits the proliferation and induces the apoptosis of NB4 cells through the regulation of the expression levels of genes involved in the NF‑κB signaling pathway.

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1	Sassano A and Platanias LC: Statins in tumor suppression. Cancer Lett. 260:11–19. 2008.
2	Hindler K, Cleeland CS, Rivera E and Collard CD: The role of statins in cancer therapy. Oncologist. 11:306–315. 2006.
3	Sivaprasad U, Abbas T and Dutta A: Differential efficacy of 3-hydroxy-3-methylglutaryl CoA reductase inhibitors on the cell cycle of prostate cancer cells. Mol Cancer Ther. 5:2310–2316. 2006.
4	Campbell MJ, Esserman LJ, Zhou Y, et al: Breast cancer growth prevention by statins. Cancer Res. 66:8707–8714. 2006.
5	Martirosyan A, Clendening JW, Goard CA and Penn LZ: Lovastatin induces apoptosis of ovarian cancer cells and synergizes with doxorubicin: potential therapeutic relevance. BMC Cancer. 10:1032010.
6	Sassano A, Katsoulidis E, Antico G, et al: Suppressive effects of statins on acute promyelocytic leukemia cells. Cancer Res. 67:4524–4532. 2007.
7	Escárcega RO, Fuentes-Alexandro S, García-Carrasco M, Gatica A and Zamora A: The transcription factor nuclear factor-kappa B and cancer. Clin Oncol (R Coll Radiol). 19:154–161. 2007.
8	Bharti AC and Aggarwal BB: Nuclear factor-kappa B and cancer: its role in prevention and therapy. Biochem Pharmacol. 64:883–888. 2002.
9	Ahn KS, Sethi G and Aggarwal BB: Reversal of chemoresistance and enhancement of apoptosis by statins through down-regulation of the NF-kappaB pathway. Biochem Pharmacol. 75:907–913. 2008.
10	Dai Y, Khanna P, Chen S, Pei XY, Dent P and Grant S: Statins synergistically potentiate 7-hydroxystaurosporine (UCN-01) lethality in human leukemia and myeloma cells by disrupting Ras farnesylation and activation. Blood. 109:4415–4423. 2007.
11	Tomiyama N, Matzno S, Kitada C, Nishiguchi E, Okamura N and Matsuyama K: The possibility of simvastatin as a chemotherapeutic agent for all-trans retinoic acid-resistant promyelocytic leukemia. Biol Pharm Bull. 31:369–374. 2008.
12	van der Weide K, de Jonge-Peeters SD, Kuipers F, de Vries EG and Vellenga E: Combining simvastatin with the farnesyltransferase inhibitor tipifarnib results in an enhanced cytotoxic effect in a subset of primary CD34⁺ acute myeloid leukemia samples. Clin Cancer Res. 15:3076–3083. 2009.
13	Toubi E and Shoenfeld Y: Toll-like receptors and their role in the development of autoimmune diseases. Autoimmunity. 37:183–188. 2004.
14	Bassères DS and Baldwin AS: Nuclear factor-kappaB and inhibitor of kappaB kinase pathways in oncogenic initiation and progression. Oncogene. 25:6817–6830. 2006.
15	Courtois G and Gilmore TD: Mutations in the NF-kappaB signaling pathway: implications for human disease. Oncogene. 25:6831–6843. 2006.
16	Pasare C and Medzhitov R: Toll-like receptors: linking innate and adaptive immunity. Adv Exp Med Biol. 560:11–18. 2005.
17	Suzuki N, Suzuki S, Duncan GS, et al: Severe impairment of interleukin-1 and Toll-like receptor signalling in mice lacking IRAK-4. Nature. 416:750–756. 2002.
18	Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z and Matsumoto K: The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature. 398:252–256. 1999.