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http://dx.doi.org/10.14348/molcells.2015.0037

Quercetin Enhances Cisplatin Sensitivity of Human Osteosarcoma Cells by Modulating microRNA-217-KRAS Axis  

Zhang, Xian (Department of Orthopaedics, the First Hospital Affiliated of Henan University)
Guo, Qinggong (Department of Orthopaedics, the First Hospital Affiliated of Henan University)
Chen, Jingtao (Department of Orthopaedics, the First Hospital Affiliated of Henan University)
Chen, Zhaohui (Department of Orthopaedics, the First Hospital Affiliated of Henan University)
Publication Information
Molecules and Cells / v.38, no.7, 2015 , pp. 638-642 More about this Journal
Abstract
Quercetin can suppress osteosarcoma cell growth and metastasis. However, other effects of quercetin on osteosarcoma remain largely unknown. This research aims to evaluate the effects of quercetin in combination with cisplatin as treatment for osteosarcoma and investigate its regulatory mechanism. Cell viability and apoptosis in 143B cell line were determined after treatment with quercetin and/or cisplatin. RT-PCR and Western blot analysis were performed to determine the RNA or protein expression levels. Moreover, transwell assay was used to evaluate metastasis. Furthermore, rescue experiments were performed to investigate the potential regulatory mechanism of the treatment. Results showed that quercetin with concentration that was equal to or greater than $10{\mu}M$ inhibited 143B proliferation, while $5{\mu}M$ quercetin enhanced the cisplatin sensitivity of 143B cells. Expression of miR-217 was upregulated after quercetin and/or cisplatin treatment, while its target KRAS was downregulated both at mRNA and protein levels. MiR-217 knockdown led to the loss of enhanced cisplatin sensitivity while miR-217 overexpression showed the opposite effects, indicating that quercetin regulated cisplatin sensitivity by modulating the miR-217-KRAS axis. In conclusion, $5{\mu}M$ quercetin enhanced the cisplatin sensitivity by modulating the miR-217-KRAS axis. This finding suggests that quercetin may be administered with cisplatin to improve the treatment for osteosarcoma.
Keywords
cisplatin; KRAS; microRNA-217; osteosarcoma; quercetin;
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1 Berndt, K., Campanile, C., Muff, R., Strehler, E., Born, W., and Fuchs, B. (2013). Evaluation of quercetin as a potential drug in osteosarcoma treatment. Anticancer Res. 33, 1297-1306.
2 Bielack, S.S., Carrle, D., Hardes, J., Schuck, A., and Paulussen, M. (2008). Bone tumors in adolescents and young adults. Curr. Treat Options Oncol. 9, 67-80.   DOI   ScienceOn
3 Chou, A.J., Gupta, R., Bell, M.D., Riewe, K.O., Meyers, P.A., and Gorlick, R. (2013). Inhaled lipid cisplatin (ILC) in the treatment of patients with relapsed/progressive osteosarcoma metastatic to the lung. Pediatr. Blood Cancer 60, 580-586.   DOI   ScienceOn
4 Galluzzi, L., Senovilla, L., Vitale, I., Michels, J., Martins, I., Kepp, O., Castedo, M., and Kroemer, G. (2012). Molecular mechanisms of cisplatin resistance. Oncogene 31, 1869-1883.   DOI   ScienceOn
5 Guo, J.H., Feng, Z.J., Huang, Z., Wang, H.Y., and Lu, W.J. (2014). MicroRNA-217 functions as a tumour suppressor gene and correlates with cell resistance to cisplatin in lung cancer. Mol. Cells 37, 664-671.   DOI   ScienceOn
6 Kato, M., Putta, S., Wang, M., Yuan, H., Lanting, L., Nair, I., Gunn, A., Nakagawa, Y., Shimano, H., Todorov, I., et al. (2009). TGFbeta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN. Nat. Cell Biol. 11, 881-U263.   DOI   ScienceOn
7 Kim, J.Y., Kim, E.H., Park, S.S., Lim, J.H., Kwon, T.K., and Choi, K.S. (2008). Quercetin sensitizes human hepatoma cells to TRAIL-induced apoptosis via Sp1-mediated DR5 upregulation and proteasome-mediated c-FLIPS down-regulation. J. Cell Biochem. 105, 1386-1398.   DOI   ScienceOn
8 Li, N., Sun, C., Zhou, B., Xing, H., Ma, D., Chen, G., and Weng, D. (2014). Low concentration of quercetin antagonizes the cytotoxic effects of anti-neoplastic drugs in ovarian cancer. PLoS One 9, e100314.   DOI   ScienceOn
9 Liang, W., Li, X., Li, C., Liao, L., Gao, B., Gan, H., Yang, Z., and Chen, X. (2011). Quercetin-mediated apoptosis via activation of the mitochondrial-dependent pathway in MG-63 osteosarcoma cells. Mol. Med. Rep. 4, 1017-1023.
10 Martinez-Velez, N., Xipell, E., Jauregui, P., Zalacain, M., Marrodan, L., Zandueta, C., Vera, B., Urquiza, L., Sierrasesumaga, L., Julian, M.S., et al. (2014). The oncolytic adenovirus Delta24-RGD in combination with cisplatin exerts a potent antiosteosarcoma activity. J. Bone Miner Res. 29, 2287-2296.   DOI   ScienceOn
11 Orsolic, N., and Car, N. (2014). Quercetin and hyperthermia modulate cisplatin-induced DNA damage in tumor and normal tissues in vivo. Tumour. Biol. 35, 6445-6454.   DOI
12 Scambia, G., Ranelletti, F.O., Benedetti Panici, P., Bonanno, G., De Vincenzo, R., Piantelli, M., and Mancuso, S. (1990). Synergistic antiproliferative activity of quercetin and cisplatin on ovarian cancer cell growth. Anticancer Drugs 1, 45-48.   DOI
13 Wang, P., Vadgama, J.V., Said, J.W., Magyar, C.E., Doan, N., Heber, D., and Henning, S.M. (2014). Enhanced inhibition of prostate cancer xenograft tumor growth by combining quercetin and green tea. J. Nutr. Biochem. 25, 73-80.   DOI   ScienceOn
14 Shen, D.W., Pouliot, L.M., Hall, M.D., and Gottesman, M.M. (2012). Cisplatin resistance: a cellular self-defense mechanism resulting from multiple epigenetic and genetic changes. Pharmacol. Rev. 64, 706-721.   DOI
15 SS, B. (2012). A review of quercetin: Antioxidant and anticancer properties. World J. Pharm. Pharm. Sci. 1, 146-160.
16 Suh, D.K., Lee, E.J., Kim, H.C., and Kim, J.H. (2010). Induction of G(1)/S phase arrest and apoptosis by quercetin in human osteosarcoma cells. Arch. Pharm. Res. 33, 781-785.   DOI   ScienceOn
17 Wu, J., Liao, Q., He, H., Zhong, D., and Yin, K. (2014). TWIST interacts with beta-catenin signaling on osteosarcoma cell survival against cisplatin. Mol. Carcinog. 53, 440-446.   DOI   ScienceOn
18 Xie, X.B., Yin, J.Q., Jia, Q., Wang, J., Zou, C.Y., Brewer, K.J., Colombo, C., Wang, Y.F., Huang, G., and Shen, J.N. (2011). Quercetin induces apoptosis in the methotrexate-resistant osteosarcoma cell line U2-OS/MTX300 via mitochondrial dysfunction and dephosphorylation of Akt. Oncol. Rep. 26, 687-693.
19 Yi, L., Zongyuan, Y., Cheng, G., Lingyun, Z., Guilian, Y., and Wei, G. (2014). Quercetin enhances apoptotic effect of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in ovarian cancer cells through reactive oxygen species (ROS) mediated CCAAT enhancer-binding protein homologous protein (CHOP)-death receptor 5 pathway. Cancer Sci. 105, 520-527.   DOI   ScienceOn
20 Zhao, W.G., Yu, S.N., Lu, Z.H., Ma, Y.H., Gu, Y.M., and Chen, J. (2010). The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis 31, 1726-1733.   DOI   ScienceOn
21 Zhao, G.Y., Cai, C.K., Yang, T.T., Qiu, X.C., Liao, B., Li, W., Ji, Z.W., Zhao, J., Zhao, H.E., Guo, M.J., et al. (2013). MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PLoS One 8, e53906.   DOI