JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2016, Vol. 54 ›› Issue (7): 18-22.doi: 10.6040/j.issn.1671-7554.0.2015.610

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Pulsatilla saponin D combined with sorafenib against hepatocellular carcinoma cell invasion and metastasis

HE Wubin1, SU Rongjian2   

  1. 1. Biological Therapy Central Laboratory, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, Liaoning, China;
    2. Life Science Institute of Jinzhou Medical University, Jinzhou 121001, Liaoning, China
  • Received:2015-06-24 Online:2016-07-10 Published:2016-07-10

Abstract: Objective To investigate the effect of Pulsatilla saponin D and sorafenib on the invasion and metastasis of human hepatoma cell line. Methods The human hepatoma cell line SMMC-7721 cells were divided into Pulsatilla saponin D group(11.9 μg/L), sorafenib group(2.15 μmol/L), combined group(Pulsatilla saponin D 11.9 μg/L+Sorafenib 2.15 μmol/L)and control group(ordinary culture). The inhibitory effects on the migration and invasion of SMMC-7721 cells were observed with MTT assay and Transwell chamber experiments. The effects on CD44V6, VEGF-C, MMP-9 gene protein expressions were detected with immunocytochemistry. Results MTT assay showed that Pulsatilla saponin D, sorafenib, and combined therapy inhibited the proliferation of SMMC-7721 cells, and the 24 h inhibition rate was less than 15%. Transwell chamber experiments showed that the adhesion inhibition rate of the combined group displayed a synergistic effect compared with the monotherapy groups, but not in a time-dependent manner; the invasion and migration inhibition rate of the combined group were significantly higher than those of the monotherapy groups(P<0.01). Immunohistochemistry results showed that the combined group had lower CD44V6, VEGF-C, and MMP-9 expressions than the monotherapy groups(P<0.05). Conclusion Pulsatilla saponin D and sorafenib synergistically inhibit the SMMC-7721 cell invasion and metastasis, and the combined effect of Pulsatilla saponin D and sorafenib is 山 东 大 学 学 报 (医 学 版)54卷7期 -贺武斌,等.白头翁皂苷D联合索拉非尼对人肝癌细胞侵袭与转移的影响 \=-better than the single drug.

Key words: Pulsatilla saponin D, Sorafenib, Invasion, Hepatoma cells, Metastasis

CLC Number: 

  • R735.7
[1] Li Y, Xu D, Bao C, et al. MicroRNA-135b, a HSF1 target, promotes tumor invasion and metastasis by regulating RECK and EVI5 in hepatocellular carcinoma[J]. Oncotarget, 2015, 6(4): 2421-2433.
[2] He G, Hu S, Zhang D, et al. Hypermethylation of FOXD3 suppresses cell proliferation, invasion and metastasis in hepatocellular carcinoma[J]. Exp Mol Pathol, 2015, 99(2): 374-382.
[3] Gao Y, Ruan B, Liu W, et al. Knockdown of CD44 inhibits the invasion and metastasis of hepatocellular carcinoma both in vitro and in vivo by reversing epithelial-mesenchymal transition[J]. Oncotarget, 2015, 6(10): 7828-7837.
[4] Zhang Z, Zhang Y, Sun XX, et al. MicroRNA-146a inhibits cancer metastasis by downregulating VEGF through dual pathways in hepatocellular carcinoma[J]. Mol Cancer, 2015, 14: 5. doi: 10.1186/1476-4598-14-5.
[5] 宋长城, 吕祥, 程彬彬, 等. 蜂毒素对人肝癌SMMC-7721细胞裸鼠皮下移植瘤生长及肿瘤血管生成的影响[J]. 癌症, 2007, 26(12): 1315-1322. SONG Changcheng, LÜ Xiang, CHENG Binbin, et al. Effects of melittin on growth and angiogenesis of human hepatocellular carcinoma SMMC-7721 cell xenografts in nude mice[J]. Chinese Journal of Cancer, 2007, 26(12): 1315-1322.
[6] 黄挺, 陈震, 杨雪飞, 等. 康莱特注射液抗恶性肿瘤肝转移疗效及机理的实验研究[J]. 中华中医药学刊, 2009, 27(3): 509-511. HUANG Ting, CHEN Zhen, YANG Xuefei, et al. A research on the kanglaite injection in treating the liver metastasis[J]. Chinese Archives of Traditional Chinese Medicine, 2009, 27(3): 509-511.
[7] Son MK, Jung KH, Hong SW, et al. SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway[J]. Food Chem, 2013, 136(1): 26-33.
[8] Hong SW, Jung KH, Lee HS, et al. SB365, Pulsatilla saponin D targets c-Met and exerts antiangiogenic and antitumor activities[J]. Carcinogenesi, 2013, 34(9): 2156-2169.
[9] 黄艳, 吴春婷, 郭红娟, 等. 人核因子κBp65核定位信号缺失突变对A549细胞恶性表型的影响[J]. 中国呼吸与危重监护杂志, 2015, 14(1): 50-59. HUANG Yan, WU Chunting, GUO Hongjuan, et al. The influence of human NF-κBp65 NLS deletion mutant plasmids on malignant phenotype of A549 lung cancer cells[J]. Chin J Respir Crit Care Med, 2015, 14(1): 50-59.
[10] An C, Choi YA, Choi D, et al. Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease[J]. Clin Mol Hepatol, 2015, 21(3): 279-286.
[11] 付伟, 高文娟, 张志勉, 等. 罗勒多糖对卵巢癌SKOV3细胞VEGF受体表达的调控作用及对其侵袭能力的影响[J]. 山东大学学报(医学版), 2014, 52(5): 664-667. FU Wei, GAO Wenjuan, ZHANG Zhimian, et al. Regulation SKOV3 cells of vascular endothelial growth factor receptors expression in by basil polysaccharide and its effect on SKOV3 cell invasion[J]. Journal of Shandong University(Health Sciences), 2014, 52(5): 664-667.
[12] 段思佳, 曾庆黎, 周凯, 等. 利用组织芯片研究VEGF-C和MMP-9在大肠癌中的表达及其意义[J]. 中国普通外科杂志, 2012, 21(4): 427-431. DUAN Sijia, ZENG Qingli, ZHOU Kai, et al. Expressions of VEGF-C and MMP-9 in colorectal cancer and their clinical relevance: a tissue microarray analysis[J]. Chinese Journal of General Surgery, 2012, 21(4): 427-431.
[13] Wang W, Iyer NG, Tay HT, et al. Microarray profiling shows distinct differences between primary tumors and commonly used preclinical models in hepatocellular carcinoma[J]. BMC Cancer, 2015, 15: 828. doi: 10.1186/S12885-015-1814-8.
[14] Son MK, Jung KH, Hong SW, et al. SB365, Pulsatilla saponin D suppresses the proliferation of human colon cancer cells and induces apoptosis by modulating the AKT/mTOR signalling pathway[J]. Food Chem, 2013, 136(1): 26-33.
[15] Won S, Jung KH, Lee HS, et al. SB365, Pulsatilla saponin D, targets c-Met and exerts antiangiogenic and antitumor activities[J]. Carcinogenesis, 2013, 34(9): 2156-2169.
[16] de Stefano G, Farella N, Scognamiglio U, et al. Sorafenib after RFA in HCC patients: a pilot study[J]. Hepatogastroenterology, 2015, 62(138): 261-263.
[17] Pal HC, Diamond AC, Strickland LR, et al. Fisetin, a dietary flavonoid, augments the anti-invasive and anti-metastatic potential of sorafenib in melanoma[J]. Oncotarget, 2015, 6(11): 6237-1-10. doi: 10.18632/oncotarget.6237.
[18] Wu X, Yang Y, Xu Z, et al. Raf kinase inhibitor protein mediated signaling inhibits invasion and metastasis of hepatocellular carcinoma[J]. Biochim Biophys Acta, 2016, 1860(2): 384-391.
[19] Zhao S, Li H, Wang Q, et al. The role of c-Src in the invasion and metastasis of hepatocellular carcinoma cells induced by association of cell surface GRP78 with activated α2M[J]. BMC Cancer, 2015, 15: 389. doi: 10.1186/S12885-015-1401-2.
[20] Mima K, Okabe H, Ishimoto T, et al. The expression levels of CD44v6 are correlated with the invasiveness of hepatocellular carcinoma in vitro, but do not appear to be clinically significant[J]. Oncol Lett, 2012, 3(5): 1047-1051.
[21] Zhuang PY, Shen J, Zhu XD, et al. Prognostic roles of cross-talk between peritumoral hepatocytes and stromal cells in hepatocellular carcinoma involving peritumoral VEGF-C, VEGFR-1 and VEGFR-3[J]. PLoS One, 2013, 8(5): e64598. doi: 10.1371/journal.pone.0064598.
[22] Chen JS, Huang XH, Wang Q, et al. Sonic hedgehog signaling pathway induces cell migration and invasion through focal adhesion kinase/AKT signaling-mediated activation of matrix metalloproteinase(MMP)-2 and MMP-9 in liver cancer[J]. Carcinogenesis, 2013, 34(1): 10-19.
[23] Kolli-Bouhafs K, Boukhari A, Abusnina A, et al. Thymoquinone reduces migration and invasion of human glioblastoma cells associated with FAK, MMP-2 and MMP-9 down-regulation[J]. Invest New Drugs, 2012, 30(6): 2121-2131.
[24] Du Y, Zhang D, Liu H, et al. Thermochemotherapy effect of nanosized As2O3/Fe3O4 complex on experimental mouse tumors and its influence on the expression of CD44v6, VEGF-C and MMP-9[J]. BMC Biotechnol, 2009, 9: 84. doi: 10.1186/1472-6750-9-84.
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