肝细胞癌对三氧化二砷的化疗耐药性机制

doi:10.3760/cma.j.issn.1673-422X.2016.11.016

国际肿瘤学杂志 ›› 2016, Vol. 43 ›› Issue (11): 861-864.doi: 10.3760/cma.j.issn.1673-422X.2016.11.016

肝细胞癌对三氧化二砷的化疗耐药性机制

陈耀庭，胡晓俊，李丹，单鸿

519000 珠海，中山大学附属第五医院介入医学中心（陈耀庭、单鸿）；中山大学孙逸仙纪念医院介入放射科（陈耀庭）；中山大学介入放射学研究所（胡晓俊、李丹、单鸿）

收稿日期:2016-03-28 出版日期:2016-11-08 发布日期:2016-11-02
通讯作者: 单鸿，Email: shanhong@mail.sysu.edu.cn E-mail:shanhong@mail.sysu.edu.cn
基金资助:
国家自然科学基金（81430041）

Chemotherapy drug resistance mechanisms of hepatocellular carcinoma to arsenic trioxide

Chen Yaoting, Hu Xiaojun, Li Dan, Shan Hong

Center for Interventional Medicine, Fifth Affiliated Hospital of Sun Yatsen University, Zhuhai 519000, China; Department of Interventional Radiology, Sun Yatsen Memorial Hospital, Sun Yatsen University, Guangzhou 510120, China

Received:2016-03-28 Online:2016-11-08 Published:2016-11-02
Contact: Shan Hong E-mail:shanhong@mail.sysu.edu.cn
Supported by:
National Natural Science Foundation of China (81430041)

摘要/Abstract

摘要： 研究证实三氧化二砷（As2O3）单药治疗肝细胞癌（HCC）的效果有限，多数学者认为主要与HCC的化疗耐药有关。HCC对As2O3的耐药机制目前仍很不明确，研究显示与As2O3的代谢特点、肝癌组织学和分子生物学的特征等密切相关。

关键词: 肝肿瘤, 砷剂, 抗药性, 肿瘤, 分子靶向治疗

Abstract: Many studies have proven that arsenic trioxide (As2O3) as a single agent is not effective against hepatocellular carcinoma (HCC). Many scholars believe that chemotherapy drug resistance of HCC to As2O3 is the most important reason. The underlying drug resistance mechanism of HCC cells to As2O3 remains unclear. Studies show that potential mechanism may be tightly associated with As2O3 pharmacokinetics and properties of HCC tissues and complex molecular biology.

Key words: Liver neoplasms, Arsenicals, Drug resistance, neoplasm, Molecular targeted therapy

陈耀庭，胡晓俊，李丹，单鸿. 肝细胞癌对三氧化二砷的化疗耐药性机制[J]. 国际肿瘤学杂志, 2016, 43(11): 861-864.

Chen Yaoting, Hu Xiaojun, Li Dan, Shan Hong. Chemotherapy drug resistance mechanisms of hepatocellular carcinoma to arsenic trioxide[J]. Journal of International Oncology, 2016, 43(11): 861-864.

参考文献

［1］ Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012［J］. CA Cancer J Clin, 2015, 65(2): 87-108. DOI: 10.3322/caac.21262. ［2］ Bruix J, Takayama T, Mazzaferro V, et al. Adjuvant sorafenib for hepatocellular carcinoma after resection or ablation (STORM): a phase 3, randomised, doubleblind, placebocontrolled trial［J］. Lancet Oncol, 2015, 16(13): 1344-1354. DOI: 10.1016/S14702045(15) 001989. ［3］ de The H, Le Bras M, LallemandBreitenbach V. The cell biology of disease: acute promyelocytic leukemia, arsenic, and PML bodies［J］. J Cell Biol, 2012, 198(1): 11-21. DOI: 10.1083/jcb.201112044. ［4］ Emadi A, Gore SD. Arsenic trioxidean old drug rediscovered［J］. Blood Rev, 2010, 24(45): 191199. DOI: 10.1016/j.blre.2010.04.001. ［5］ Zhang X, Yang XR, Sun C, et al. Promyelocytic leukemia protein induces arsenic trioxide resistance through regulation of aldehyde dehydrogenase 3 family member A1 in hepatocellular carcinoma［J］. Cancer Lett, 2015, 366(1): 112122. DOI: 10.1016/j.canlet.2015.06.014. ［6］ Zheng T, Yin D, Lu Z, et al. Nutlin3 overcomes arsenic trioxide resistance and tumor metastasis mediated by mutant p53 in hepatocellular carcinoma［J］. Mol Cancer, 2014, 13(5): 133-144. DOI: 10.1186/1476-4598-13-133. ［7］ Maeda H, Nakamura H, Fang J. The EPR effect for macromolecular drug delivery to solid tumors: improvement of tumor uptake, lowering of systemic toxicity, and distinct tumor imaging in vivo［J］. Adv Drug Deliv Rev, 2013, 65(1): 71-79. DOI: 10.1016/j.addr.2012.10.002. ［8］ Hua H, Qin S, Rui J, et al. Pharmacokinetics of arsenic trioxide (As(2)O(3)) in Chinese primary hepatocarcinoma patients［J］. Asian Pac J Cancer Prev, 2011, 12(1): 61-65. DOI: http://dx.doi.org/10.7314/APJCP.2011.12.1.61. ［9］ Ahn RW, Chen F, Chen H, et al. A novel nanoparticulate formulation of arsenic trioxide with enhanced therapeutic efficacy in a murine model of breast cancer［J］. Clin Cancer Res, 2010, 16(14): 3607-3617. DOI: 10.1158/1078-0432.CCR-10-0068. ［10］ Qian C, Wang Y, Chen Y, et al. Suppression of pancreatic tumor growth by targeted arsenic delivery with antiCD44v6 single chain antibody conjugated nanoparticles［J］. Biomaterials, 2013, 34(26): 6175-6184. DOI: 10.1016/j.biomaterials.2013.04.056. ［11］ Wilson GK, Tennant DA, McKeating JA. Hypoxia inducible factors in liver disease and hepatocellular carcinoma: current understanding and future directions［J］. J Hepatol, 2014, 61(6): 13971406. DOI: 10.1016/j.jhep.2014.08.025. ［12］ Warfel NA, ElDeiry WS. HIF1 signaling in drug resistance to chemotherapy［J］. Curr Med Chem, 2014, 21(26): 3021-3028. DOI: 10.2174/0929867321666140414101056. ［13］ Poller B, Wagenaar E, Tang SC, et al. Doubletransduced MDCKⅡ cells to study human Pglycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) interplay in drug transport across the bloodbrain barrier［J］. Mol Pharm, 2011, 8(2): 571-582. DOI: 10.1021/mp1003898. ［14］ Cao Y, Eble JM, Moon E, et al. Tumor cells upregulate normoxic HIF1alpha in response to doxorubicin［J］. Cancer Res, 2013, 73(20): 6230-6242. DOI: 10.1158/0008-5472.CAN-12-1345. ［15］ Liang Y, Zheng T, Song R, et al. Hypoxiamediated sorafenib resistance can be overcome by EF24 through Von HippelLindau tumor suppressordependent HIF1alpha inhibition in hepatocellular carcinoma［J］. Hepatology, 2013, 57(5): 1847-1857. DOI: 10.1002/hep.26224. ［16］ Liu Y, Zhang JB, Qin Y, et al. PROX1 promotes hepatocellular carcinoma metastasis by way of upregulating hypoxiainducible factor 1alpha expression and protein stability［J］. Hepatology, 2013, 58(2): 692705. DOI: 10.1002/hep.26398. ［17］ Li J, Xu Y, Long XD, et al. Cbx4 governs HIF1alpha to potentiate angiogenesis of hepatocellular carcinoma by its SUMO E3 ligase activity［J］. Cancer Cell, 2014, 25(1): 118-131. DOI: 10.1016/j.ccr.2013.12.008. ［18］ Khoo KH, Verma CS, Lane DP. Drugging the p53 pat hway: understanding the route to clinical efficacy［J］. Nat Rev Drug Discov, 2014, 13(3): 217-236. DOI: 10.1038/nrd4236. ［19］ He X, Liao J, Liu F, et al. Functional repair of p53 mutation in colorectal cancer cells using transsplicing［J］. Oncotarget, 2015, 6(4): 2034-2045. DOI: 10.18632/oncotarget.2988. ［20］ Gamell C, Jan Paul P, Haupt Y, et al. PML tumour suppression and beyond: therapeutic implications［J］. FEBS Lett, 2014, 588(16): 2653-2662. DOI: 10.1016/j.febslet.2014.02.007. ［21］ Liu ZM, Tseng JT, Hong DY, et al. Suppression of TGinteracting factor sensitizes arsenic trioxideinduced apoptosis in human hepatocellular carcinoma cells［J］. Biochem J, 2011, 438(2): 349-358. DOI: 10.1042/BJ20101653. ［22］ Guo XL, Li D, Sun K, et al. Inhibition of autophagy enhances anticancer effects of bevacizumab in hepatocarcinoma［J］. J Mol Med (Berl), 2013, 91(4): 473483. DOI: 10.1007/s00109-012-0966-0. ［23］ Cojoc M, Mabert K, Muders MH, et al. A role for cancer stem cells in therapy resistance: cellular and molecular mechanisms［J］. Semin Cancer Biol, 2015, 31: 1627. DOI: 10.1016/j.semcancer.2014.06.004. ［24］ Rangwala F, Williams KP, Smith GR, et al. Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines［J］. BMC Cancer, 2012, 12(9): 402-412. DOI: 10.1186/1471-2407-12-402. ［25］ Hernanda PY, PedrozaGonzalez A, van der Laan LJ, et al. Tumor promotion through the mesenchymal stem cell compartment in human hepatocellular carcinoma［J］. Carcinogenesis, 2013, 34(10):2330-2340. DOI: 10.1093/carcin/bgt210. ［26］ He J, Wang M, Jiang Y, et al. Chronic arsenic exposure and angiogenesis in human bronchial epithelial cells via the ROS/miR-199a 5p/HIF-1alpha/COX-2 pathway［J］. Environ Health Perspect, 2014, 122(3): 255261. DOI: 10.1289/ehp.1307545. ［27］ Subbarayan PR, Ardalan B. In the war against solid tumors arsenic trioxide needs partners［J］. J Gastrointest Cancer, 2014, 45(3): 363-371. DOI: 10.1007/s12029-014-9617-8. ［28］ Liu B, Huang JW, Li Y, et al. Arsenic trioxide transarterial chemoembolization with and without additional intravenous administration of arsenic trioxide in unresectable hepatocellular carcinoma with lung metastasis: a singleblind, randomized trial［J］. J Cancer Res Clin Oncol, 2015, 141(6): 1103-1108. DOI: 10.1007/s00432-014-1866-1.

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肝细胞癌对三氧化二砷的化疗耐药性机制

Chemotherapy drug resistance mechanisms of hepatocellular carcinoma to arsenic trioxide

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