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Article Navigation >  Journal of Pharmaceutical Practice and Service  > 2015  >  33(2): 138-142

HE Wenting, GONG Zhirong, SUN Zhiguo, WANG Meiping, GAO Jie, ZHONG Yanqiang, LU Ying. Synergic effects of sorafenib combined with sulforaphane against hepatocellular carcinoma cells in vitro[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(2): 138-142. doi: 10.3969/j.issn.1006-0111.2015.02.012
Citation: HE Wenting, GONG Zhirong, SUN Zhiguo, WANG Meiping, GAO Jie, ZHONG Yanqiang, LU Ying. Synergic effects of sorafenib combined with sulforaphane against hepatocellular carcinoma cells in vitro[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(2): 138-142. doi: 10.3969/j.issn.1006-0111.2015.02.012
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Synergic effects of sorafenib combined with sulforaphane against hepatocellular carcinoma cells in vitro

doi: 10.3969/j.issn.1006-0111.2015.02.012
  • 1.

    Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China

  • 2.

    Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

  • 3.

    Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China;Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, China

  • Received Date: 2014-09-28
  • Rev Recd Date: 2014-12-26
  • Objective To investigate the synergic ratio of sorafenib (SO) and sulforaphane (SF) against the hepatocellular carcinoma cell line HepG2 in vitro. Methods The synergic effect of SO combined with SF against HepG2 cells was determined by the CCK8 assay (the synergic effect was determined by combination index (CI) value: CI>1.1, antagonistic; 0.9Results The CCK-8 assay showed that SO combined with SF at the molar rate of 1:1,1:10 and 1:20 exhibited strong antagonism (CI>1.1), whereas 20:1,5:1 and 1:5 ratio resulted in synergistic activity (CI<0.9). Furthermore, 10:1 ratio acted as an additive effective (0.9P<0.01). The early and late apoptosis rate of HepG2 cells (21.71±6.06) of the group treated with SO combined with SF at 5:1 synergistic ratio was significantly higher than that of the group treated with SO combined with SF at 1:1 antagonistic ratio(6.64±0.311)(P<0.01). Conclusion SO combined with SF at the molar rate of 5:1 can synergistically inhibit the growth of hepatocellular carcinoma cell line HepG2 in vitro.
  • [1] Wilhelm SM,Adnane L,Newell P,et al.Preclinical over view of sorafenib,a multikinase inhibitor that targets both Raf and VEGF and PDGF receptor tyrosine kinase signaling[J].Mol Cancer Ther,2008,7(10):3129 3140.
    [2] Paez-Ribes M, Allen E, Hudock J, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis[J].Cancer Cell,2009,15(3):220 231.
    [3] Ebos JM, Lee CR, Cruz-Munoz W, et al. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis[J]. Cancer Cell,2009,15(3):232 239.
    [4] Rausch V, Lui L, Kallifatidis G, et al. Synergistic activity of sorafenib and sulforaphane abolishes pancreatic cancer stem cell characteristics[J]. Cancer Res,2010,70(12):5004-5013.
    [5] Choi S, Lew KL, Xiao H, et al. D,L-Sulforaphane-induced cell death in human prostate cancer cells is regulated by inhibitor of apoptosis family proteins and Apaf-1[J]. Carcinogenesis,2007,28(1):151 162.
    [6] Xu C, Shen G, Chen C, et al. Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells[J]. Oncogene,2005,24(28):4486-4495.
    [7] Jeong WS, Kim IW, Hu R,et al. Modulatory properties of various natural chemopreventive agents on the activation of NF-kappaB signaling pathway[J]. Pharm Res,2004,21(4):661 670.
    [8] Tardi P, Johnstone S, Harasym N,et al. In vivo maintenance of synergistic cytarabine:daunorubicin ratios greatly enhances therapeutic efficacy[J].Leuk Res,2009,33(1):129-139.
    [9] Kupsch P, Henning B, Passarge K, et al. Results of a phase Ⅰ trial of sorafenib (BAY 43-9006) in combination with oxaliplatin in patients with refractory solid tumors, including colorectal cancer[J]. Clin Colorectal Cancer, 2005,5(3):188-196.
    [10] Lee J, Kang WK, Kwon JM, et al.Phase Ⅱ trial of irinotecan plus oxaliplatin and 5-fluorouracil/leucovorin in patients with untreated metastatic gastric adenocarcinoma.[J].Ann Oncol,2007,18(1):88-92.
    [11] Richly H, Henning B, Kupsch P, et al. Results of a phase Ⅰ trial of sorafenib (BAY 43-9006) in combination with doxorubicin in patients with refractory solid tumors[J]. Ann Oncol,2006,17(5):866 873.
    [12] Jonge MJA, Dumez H,Kitzen JEM, et al. Phase Ⅰ safety and pharmacokinetic study of SU-014813 in combination with docetaxel in patients with advanced solid tumours[J].Eur J Cancer,2011,47(9):1328-1335.
    [13] Flaherty KT, Lee SJ, Zhao F, et al.Phase Ⅲ trial of carboplatin and paclitacel with or without sorafenib in metastatic melanoma[J].J Clin Oncol,2013,31(3):373-379.
    [14] Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis[J].Cancer Res,2004,64(19):7099-7109.
    [15] Carlomagno F, Anaganti S, Guida T, et al. BAY 43-9006 inhibition of oncogenic RET mutants[J]. J Natl Cancer Inst, 2006,98(5):326-334.
    [16] Clarke JD, Dashwood RH, Ho E. Multi-targeted prevention of cancer by sulforaphane[J].Cancer Lett, 2008,269(2):291-304.
    [17] Zhang Y, Tang L. Discovery and development of sulforaphane as a cancer chemopreventive phytochemical[J].Acta Pharmacol Sin, 2007,28(9):1343-1354.
    [18] Pavillard V, Kherfellah D, Richard S, et al. Effects of the combination of camptothecin and doxorubicin or etoposide on rat glioma cells and camptothecin-resistant variants[J].Br J Cancer, 2001,85(7):1077-1083.
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Synergic effects of sorafenib combined with sulforaphane against hepatocellular carcinoma cells in vitro

doi: 10.3969/j.issn.1006-0111.2015.02.012
  • 1. Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China
  • 2. Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
  • 3. Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, China;Department of Pharmaceutics, School of Pharmacy, Second Military Medical University, Shanghai 200433, China
  • Received Date: 2014-09-28
  • Rev Recd Date: 2014-12-26

Abstract: Objective To investigate the synergic ratio of sorafenib (SO) and sulforaphane (SF) against the hepatocellular carcinoma cell line HepG2 in vitro. Methods The synergic effect of SO combined with SF against HepG2 cells was determined by the CCK8 assay (the synergic effect was determined by combination index (CI) value: CI>1.1, antagonistic; 0.9Results The CCK-8 assay showed that SO combined with SF at the molar rate of 1:1,1:10 and 1:20 exhibited strong antagonism (CI>1.1), whereas 20:1,5:1 and 1:5 ratio resulted in synergistic activity (CI<0.9). Furthermore, 10:1 ratio acted as an additive effective (0.9P<0.01). The early and late apoptosis rate of HepG2 cells (21.71±6.06) of the group treated with SO combined with SF at 5:1 synergistic ratio was significantly higher than that of the group treated with SO combined with SF at 1:1 antagonistic ratio(6.64±0.311)(P<0.01). Conclusion SO combined with SF at the molar rate of 5:1 can synergistically inhibit the growth of hepatocellular carcinoma cell line HepG2 in vitro.

HE Wenting, GONG Zhirong, SUN Zhiguo, WANG Meiping, GAO Jie, ZHONG Yanqiang, LU Ying. Synergic effects of sorafenib combined with sulforaphane against hepatocellular carcinoma cells in vitro[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(2): 138-142. doi: 10.3969/j.issn.1006-0111.2015.02.012
Citation: HE Wenting, GONG Zhirong, SUN Zhiguo, WANG Meiping, GAO Jie, ZHONG Yanqiang, LU Ying. Synergic effects of sorafenib combined with sulforaphane against hepatocellular carcinoma cells in vitro[J]. Journal of Pharmaceutical Practice and Service, 2015, 33(2): 138-142. doi: 10.3969/j.issn.1006-0111.2015.02.012
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