RNA干扰技术治疗肝癌的作用机制

doi:10.3760/cma.j.issn.1673-422X.2017.04.015

摘要/Abstract

摘要： 原发性肝癌是常见的恶性肿瘤之一，但是传统的治疗手段疗效并不令人满意。RNA干扰是近年来发展较快的新的治疗手段，研究发现它能够通过抑制肝癌细胞生长、增殖和促进细胞凋亡，抑制肝癌细胞侵袭和转移，抑制肿瘤新生血管生成和克服化疗耐药的途径发挥抗肿瘤作用。

关键词: 肝肿瘤, RNA干扰, 凋亡, 血管新生

Abstract: Primary liver cancer is one of the common malignant tumors. However, the efficacy of traditional treatments is not satisfactory. RNA interference is a new treatment method, which develops rapidly in recent years. It has been found that RNA interference can exert the antitumor effect through inhibiting the growth and proliferation of hepatocarcinoma cells, promoting apoptosis, inhibiting the invasion and metastasis of hepatocarcinoma cells, inhibiting angiogenesis and overcoming the resistance to chemotherapy.

Key words: Hepatocellular carcinoma, RNA interferece, Apoptosis, Angiogenesis

侯晓芸,褚燕君. RNA干扰技术治疗肝癌的作用机制[J]. 国际肿瘤学杂志, 2017, 44(4): 297-299.

Hou Xiaoyun, Chu Yanjun.. The mechanism of RNA interference for hepatocellular carcinoma treatment[J]. Journal of International Oncology, 2017, 44(4): 297-299.

参考文献

［1］ Jemal A, Bray F, Center MM, et al. Global cancer statistics［J］. CA Cancer J Clin, 2011, 61(2): 69-90. DOI: 10.3322/caac.20107. ［2］ Li L, Mu-oz-Culla M, Carmona U, et al. Ferritin-mediated siRNA delivery and gene silencing in human tumor and primary cells［J］. Biomaterials, 2016, 98: 143-151. DOI: 10.1016/j.biomaterials.2016.05.006. ［3］ PalancaWessels MC, Booth GC, Convertine AJ, et al. Antibody targeting facilitates effective intratumoral siRNA nanoparticle delivery to HER2overexpressing cancer cells［J］. Oncotarget, 2016, 7(8): 9561-9575. DOI: 10.18632/oncotarget.7076. ［4］ Vander Heiden MG, Cantley LC, Thompson CB. Understanding the warburg effect: the metabolic requirements of cell proliferation［J］. Science, 2009, 324(5930): 1029-1033. DOI: 10.1126/science.1160809. ［5］ Noguchi C, Kamitori K, Hossain A, et al. D-allose inhibits cancer cell growth by reducing GLUT1 expression［J］. Tohoku J Exp Med, 2016, 238(2): 131-141. DOI: 10.1620/tjem.238.131. ［6］ Huang Q, Li J, Xing J, et al. CD147 promotes reprogramming of glucose metabolism and cell proliferation in HCC cells by inhibiting the p53dependent signaling pathway［J］. J Hepatol, 2014, 61(4): 859-866. DOI: 10.1016/j.jhep.2014.04.035. ［7］ Amann T, Maegdefrau U, Hartmann A, et al. GLUT1 expression is increased in hepatocellular carcinoma and promotes tumorigenesis［J］. Am J Pathol, 2009, 174(4): 1544-1552. DOI: 10.2353/ajpath.2009.080596. ［8］ Cho-Rok J, Yoo J, Jang YJ, et al. Adenovirus-mediated transfer of siRNA against PTTG1 inhibits liver cancer cell growth in vitro and in vivo［J］. Hepatology, 2006, 43(5): 1042-1052. ［9］ Doan CC, Doan NT, Nguyen QH, et al. Downregulation of Kinesin spindle protein inhibits proliferation, induces apoptosis and increases chemosensitivity in hepatocellular carcinoma cells［J］. Iran Biomed J, 2015, 19(1): 1-16. ［10］ Liu W, Zhu F, Jiang Y, et al. siRNA targeting survivin inhibits the growth and enhances the chemosensitivity of hepatocellular carcinoma cells［J］. Oncol Rep, 2013, 29(3): 1183-1188. DOI: 10.3892/or.2012.2196. ［11］ Vogl TJ, Oppermann E, Qian J, et al. Transarterial chemoembolization of hepatocellular carcinoma in a rat model: the effect of additional injection of survivin siRNA to the treatment protocol［J］. BMC Cancer, 2016, 16: 325. DOI: 10.1186/s12885-016-2357-3. ［12］ Zhao A, Zeng Q, Xie X, et al. MicroRNA-125b induces cancer cell apoptosis through suppression of Bcl-2 expression［J］. J Genet Genomics, 2012, 39(1): 29-35. DOI: 10.1016/j.jgg.2011.12.003. ［13］ Fu BH, Wu ZZ, Qin J. Effects of integrin α6β1 on migration of hepatocellular carcinoma cells［J］. Mol Biol Rep, 2011, 38(5): 3271-3276. DOI: 10.1007/s11033-0100308-7. ［14］ Lv G, Lv T, Qiao S, et al. RNA interference targeting human integrin α6 suppresses the metastasis potential of hepatocellular carcinoma cells［J］. Eur J Med Res, 2013, 18: 52. DOI: 10.1186/2047-783X-18-52. ［15］ Wu JM, Xu Y, Skill NJ, et al. Autotaxin expression and its connection with the TNF-alpha-NF-kappaB axis in human hepatocellular carcinoma［J］. Mol Cancer, 2010, 9: 71. DOI: 10.1186/1476-4598-9-71. ［16］ BenBaruch A. Organ selectivity in metastasis: regulation by chemokines and their receptors［J］. Clin Exp Metastasis, 2008, 25(4): 345-356. DOI: 10.1007/s10585-007-9097-3. ［17］ Xue TC, Chen RX, Han D, et al. Down-regulation of CXCR7 inhibits the growth and lung metastasis of human hepatocellular carcinoma cells with highly metastatic potential［J］. Exp Ther Med, 2012, 3(1): 117-123. ［18］ Lu Y, Zhu M, Li W, et al. Alpha fetoprotein plays a critical role in promoting metastasis of hepatocellular carcinoma cells［J］. J Cell Mol Med, 2016, 20(3): 549-558. DOI: 10.1111/jcmm.12745. ［19］ Weis SM, Cheresh DA. Tumor angiogenesis: molecular pathways and therapeutic targets［J］. Nat Med, 2011, 17(11): 1359-1370. DOI: 10.1038/nm.2537. ［20］ Chen S, Feng J, Ma L, et al. RNA interference technology for anti-VEGF treatment［J］. Expert Opin Drug Deliv, 2014, 11(9): 1471-1480. DOI: 10.1517/17425247.2014.926886. ［21］ Zou Y, Guo CG, Zhang MM. Inhibition of human hepatocellular carcinoma tumor angiogenesis by siRNA silencing of VEGF via hepatic artery perfusion［J］. Eur Rev Med Pharmacol Sci, 2015, 19(24): 4751-4761. ［22］ Hague S, Zhang L, Oehler MK, et al. Expression of the hypoxically regulated angiogenic factor adrenomedullin correlates with uterine leiomyoma vascular density［J］. Clin Cancer Res, 2000, 6(7): 2808-2814. ［23］ Li F, Yang R, Zhang X, et al. Silencing of hypoxia-inducible adrenomedullin using RNA interference attenuates hepatocellular carcinoma cell growth in vivo［J］. Mol Med Rep, 2014, 10(3): 1295-1302. DOI: 10.3892/mmr.2014.2320. ［24］ Meng W, Li X, Bai Z, et al. Silencing alphafetoprotein inhibits VEGF and MMP-2/9 production in human hepatocellular carcinoma cell［J］. PLoS One, 2014, 9(2): e90660. DOI: 10.1371/journal.pone.0090660. ［25］ Yang T, Zheng ZM, Li XN, et al. MiR-223modulates multidrug resistance via downregulation of ABCB1 in hepatocellular carcinoma cells［J］. Exp Biol Med (Maywood), 2013, 238(9): 1024-1032. DOI: 10.1177/1535370213497321. ［26］ Su Z, Liu G, Fang T, et al. Silencing MRP1-4 genes by RNA interference enhances sensitivity of human hepatoma cells to chemotherapy［J］. Am J Transl Res, 2016, 8(6): 2790-2802. ［27］ Tang B, Hu Z, Li Y, et al. Downregulation of δ opioidreceptor by RNA interference enhances the sensitivity of BEL/FU drug-resistant human hepatocellular carcinoma cells to 5-FU［J］. Mol Med Rep, 2016, 13(1): 59-66. DOI: 10.3892/mmr.2015.4511.

[1]	陈红健, 张素青. 血清miR-24-3p、H2AFX与肝癌患者临床病理特征及术后复发的关系研究[J]. 国际肿瘤学杂志, 2024, 51(6): 344-349.
[2]	任露, 谢晓丽, 张坤, 王丽娟. 双氢青蒿素联合卡非佐米对多发性骨髓瘤细胞活性、增殖、凋亡的影响及机制研究[J]. 国际肿瘤学杂志, 2024, 51(3): 129-136.
[3]	彭琴, 蔡玉婷, 王伟. KPNA2在肝癌中的研究进展[J]. 国际肿瘤学杂志, 2024, 51(3): 181-185.
[4]	孙国宝, 杨倩, 庄庆春, 高斌斌, 孙晓刚, 宋伟, 沙丹. 结直肠癌肝转移组织病理学生长方式研究进展[J]. 国际肿瘤学杂志, 2024, 51(2): 114-118.
[5]	张科平, 赵永生, 杨娟, 付茂勇. 绿原酸通过抑制PI3K-Akt信号通路诱导肺癌A549细胞线粒体功能障碍[J]. 国际肿瘤学杂志, 2024, 51(1): 21-28.
[6]	向玉玲, 谭佳杰, 熊远果, 赵丽蓉, 黎晨, 张洪. 脱水淫羊藿素对肝癌细胞增殖、迁移和凋亡的影响[J]. 国际肿瘤学杂志, 2023, 50(9): 513-519.
[7]	冯东旭, 吴炜, 高平发, 王军, 施丽娟, 陈大伟, 李文兵, 张美峰. miR-451通过调控Rho/ROCK1信号通路对乳腺癌细胞糖酵解及凋亡的影响[J]. 国际肿瘤学杂志, 2023, 50(8): 449-456.
[8]	吴佳丽, 张佳慧, 张萍, 肖昕悦, 李睿, 张红宇. Bcl-2 BH4选择性抑制剂BDA-366抑制NK/T细胞淋巴瘤细胞的机制研究[J]. 国际肿瘤学杂志, 2023, 50(7): 413-418.
[9]	杨娅, 王慧礼, 刘艳, 郭金凤, 王春霞, 吕敏, 山长平. GCSH基因在胃癌SNU-1细胞增殖和凋亡中的作用研究[J]. 国际肿瘤学杂志, 2023, 50(5): 257-262.
[10]	李佳璇, 封颖璐. 糖皮质激素受体在肝癌细胞生长中的作用机制[J]. 国际肿瘤学杂志, 2023, 50(4): 241-243.
[11]	朱易, 陈健. 硫化氢在肿瘤发生发展中的作用机制及其供体抗肿瘤作用[J]. 国际肿瘤学杂志, 2023, 50(12): 729-733.
[12]	和婷, 王希, 张惠中, 刘昕阳, 王会平, 董轲. 血清TIM-3对肝癌患者诊断价值的研究[J]. 国际肿瘤学杂志, 2022, 49(9): 537-542.
[13]	连海伟, 杨烁锐, 刘仁忠. 金松双黄酮联合CX-4945通过Notch1通路调控胶质母细胞瘤细胞增殖与凋亡的机制研究[J]. 国际肿瘤学杂志, 2022, 49(6): 321-326.
[14]	杨娅, 宁晓飞, 李炳亮, 姚慧, 山长平, 吕敏. 原花青素通过诱导活性氧产生介导抗SNU-1胃癌细胞株的作用机制研究[J]. 国际肿瘤学杂志, 2022, 49(5): 257-262.
[15]	张玉敏, 赵现伟, 何前进, 陈杰能. 超声造影联合血清CXCL8、CXCR2在原发性肝癌经导管动脉化疗栓塞术后疗效评估中的价值分析[J]. 国际肿瘤学杂志, 2022, 49(10): 592-596.