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

doi:10.6040/j.issn.1671-7554.0.2015.610

摘要/Abstract

摘要： 目的探讨白头翁皂苷D联合索拉非尼对人肝癌细胞株侵袭和转移的影响。方法以人肝癌细胞株SMMC-7721细胞为研究对象,分为白头翁皂苷D组(浓度为11.9 μg /L)、索拉非尼组(浓度为2.15 μmol/L)、联合组(白头翁皂苷D 11.9 μg/L+索拉非尼2.15 μmol/L)以及对照组(普通培养液)。通过MTT法、Transwell小室实验观察白头翁皂苷D、索拉非尼单药和联合对SMMC-7721细胞的侵袭和转移的抑制作用,并用免疫组织化学方法检测CD_44V6、血管内皮生长因子C(VEGF-C)、基质金属蛋白酶MMP-9基因蛋白表达的影响。结果 MTT结果显示,白头翁皂苷D、索拉非尼单药和联合对SMMC-7721细胞的增殖均有抑制作用,且24 h的抑制率都<15%;Transwell小室实验结果显示,联合组的黏附抑制率与单药组相比,具有协同抑制作用,但未呈现时间依赖关系;联合组的侵袭抑制率和迁移抑制率均显著高于单药组(P<0.01);免疫组织化学结果表明,联合组在下调CD_44V6、VEGF-C、MMP-9方面均高于单药组(P<0.05)。结论白头翁皂苷D和索拉非尼联合可协同抑制SMMC-7721细胞侵袭和转移,联合效果整体优于单药。

关键词: 白头翁皂苷D, 侵袭, 转移, 肝癌细胞, 索拉非尼

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 CD_44V6, 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 CD_44V6, 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

中图分类号:

R735.7

贺武斌,苏荣健. 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[J]. 山东大学学报（医学版）, 2016, 54(7): 18-22.

HE Wubin, SU Rongjian. Pulsatilla saponin D combined with sorafenib against hepatocellular carcinoma cell invasion and metastasis[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2016, 54(7): 18-22.

参考文献

[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.

相关文章 15

[1]	殷悦,莫振飞,吴培昕,刘金霞,魏元辉,任佳博,李春笋. GPX1基因在肺癌中的表达特征及其对肺腺癌细胞增殖、迁移、侵袭、凋亡的影响[J]. 山东大学学报 (医学版), 2026, 64(1): 65-73.
[2]	韩觉明,王晖,吴倩,郑慧玲,朱琳. B4GALNT4促进肺腺癌细胞增殖、迁移和侵袭能力[J]. 山东大学学报 (医学版), 2025, 63(7): 23-31.
[3]	张洁,赵颖慧,董雅琪,李娟,李培龙,杜鲁涛. GPR133基因甲基化在早期胃癌淋巴结转移预测中的作用[J]. 山东大学学报 (医学版), 2025, 63(3): 76-84.
[4]	刘振昆,吕纪玲,徐伟伟,马力天,张才擎. BALF tNGS检测及培养对NSCLC合并IPFD的诊断价值[J]. 山东大学学报 (医学版), 2025, 63(11): 36-45.
[5]	张洁,张芳芳,王靖楠,李泽宇,宋颖,李娜. circ_0000144在乳腺癌中的表达及其对乳腺癌细胞增殖、迁移和侵袭能力的影响[J]. 山东大学学报 (医学版), 2025, 63(1): 35-42.
[6]	孙婧,杨瑞敏,王聪,张月,罗兵. 基于术前超声、炎症指标及超声影像组学联合模型预测乳腺癌腋窝淋巴结转移[J]. 山东大学学报 (医学版), 2025, 63(1): 73-80.
[7]	张学宇,张学海,孙文青,刘晗,姜金波,刘寒,李远,陈晓梅. 重症新型冠状病毒肺炎伴侵袭性肺曲霉病及反复致命性消化道出血1例[J]. 山东大学学报 (医学版), 2024, 62(7): 56-61.
[8]	宋艳艳,左淑英. 透明细胞肾细胞癌颌下腺转移1例并文献复习[J]. 山东大学学报 (医学版), 2024, 62(7): 120-124.
[9]	林雨洋,王蓓,李菲. 大于10 mm甲状腺乳头状癌侧颈区淋巴结转移预测[J]. 山东大学学报 (医学版), 2024, 62(6): 54-64.
[10]	刘爱静,李雁儒,高惠茹,段伟丽,李培龙,李娟,杜鲁涛,王传新. 自噬相关蛋白5在结肠癌中的表达及对结肠癌细胞迁移及侵袭能力的影响[J]. 山东大学学报 (医学版), 2024, 62(4): 14-23.
[11]	吴霖,石晨曦,童星. 肺良性转移性平滑肌瘤病7例并文献复习[J]. 山东大学学报 (医学版), 2024, 62(4): 78-84.
[12]	孙菁果,朱文帅,鲁艺,马晓丽,郏雁飞. 幽门螺杆菌感染对胃癌细胞m6A水平的影响及其机制[J]. 山东大学学报 (医学版), 2023, 61(9): 10-18.
[13]	董雅琪,王新慧,赵颖慧,王传新. 血清外泌体LINC02163作为结直肠癌远处转移标志物的临床价值[J]. 山东大学学报 (医学版), 2023, 61(9): 19-28.
[14]	常晴,刘佳,曲爱林,杨咏梅. 利用数据库信息分析NAMPT与肝癌的病理特征和免疫浸润的关联性[J]. 山东大学学报 (医学版), 2023, 61(4): 26-36.
[15]	郭崇勇,赵朋,刘海盟,王强, 贾宗师,张建. 胸前丘疹为首发表现的胃癌1例[J]. 山东大学学报 (医学版), 2023, 61(4): 119-120.

多维度评价

Viewed

Full text

Abstract

Cited

Shared

Discussed