乳腺癌多药耐药机制及其逆转剂的研究进展
Research Progress of Multidrug Resistance Mechanism and Reversal Agents in Breast Cancer
DOI: 10.12677/ACM.2019.912220, PDF,  被引量    国家自然科学基金支持
作者: 袁佳琪, 朱 翔, 徐杨安泰, 周轶平*：昆明医科大学药学院暨云南省天然药物药理重点实验室，云南 昆明
关键词: 乳腺癌；多药耐药；化疗；内分泌治疗；逆转剂；Breast Cancer； Multidrug Resistance； Chemotherapy； Endocrine Therapy； Reversal Agents
摘要: 乳腺癌的治疗以药物治疗为主，包括化疗和内分泌治疗，而多药耐药性的产生是药物治疗失败的主要原因。乳腺癌多药耐药性的产生，可能是P-gp高表达，PI3K/AKT/mTOR和MAPK信号通路调控异常、ER缺失等多种机制共同作用的结果。为改善乳腺癌药物治疗效果，针对其多药耐药相关机制，开发相关逆转剂成为研究热点之一。本文将综合介绍乳腺癌耐药相关机制及其逆转剂的研究进展。
Abstract: The treatment of breast cancer is mainly based on drug therapy, including chemotherapy and endocrine therapy. The emergence of multidrug resistance is the main reason for drug treatment failure. Multidrug resistance of breast cancer results from multiple mechanisms, including high expression of P-gp, abnormal regulation of PI3K/AKT/mTOR and MAPK signaling pathways, and absence of ER expression. Searching new reversal agents is one of the research hotspots in order to improve the effect of therapeutic drugs. In this paper, we summarized the mechanisms of drug resistance in breast cancer and its reversal agents.
文章引用：袁佳琪, 朱翔, 徐杨安泰, 周轶平. 乳腺癌多药耐药机制及其逆转剂的研究进展[J]. 临床医学进展, 2019, 9(12): 1421-1427. https://doi.org/10.12677/ACM.2019.912220

参考文献

[1] 赵毅, 邓鑫. 乳腺癌分子分型与治疗策略[J]. 中国实用外科杂志, 2015, 35(7): 704-708.
[2] 李惠平. 不同分子类型乳腺癌的治疗策略和治疗后管理[J]. 癌症进展, 2016, 14(12): 1166-1166.
[3] Fan, L., Strasser-Weippl, K., Li, J.J., et al. (2014) Breast Cancer in China. The Lancet Oncology, 15, e279-e289. [Google Scholar] [CrossRef] 
[4] 李明卉, 夏添松, 王水. 乳腺癌常用化疗药物的作用机制及血液学不良反应的研究进展[J]. 中华乳腺病杂志(电子版), 2017, 11(3): 186-190.
[5] Van, H.S., Sparidans, R.W., Wagenaar, E., et al. (2017) Breast Cancer Resistance Protein (BCRP/ABCG2) and P-Glycoprotein (P-gp/ABCB1) Transport Afatinib and Restrict Its Oral Availability and Brain Accumulation. Pharmacological Research, 120, 43-50. [Google Scholar] [CrossRef] [PubMed]
[6] 沈晓玲, 杨志宏. 多药耐药相关ABC转运蛋白信号转导通路研究进展[J]. 中国药理学与毒理学杂志, 2018, 32(10): 72-82.
[7] Liu, T., Guo, J.C. and Zhang, X.X. (2019) MiR-202-5p/PTEN Mediates Doxorubicin-Resistance of Breast Cancer Cells via PI3K/Akt Signaling Pathway. Cancer Biology & Therapy, 20, 1-10. [Google Scholar] [CrossRef] [PubMed]
[8] Liu, S.W., Chen, S., Yuan, W.G., et al. (2017) PD-1/PD-L1 Interaction Up-Regulates MDR1/P-gp Expression in Breast Cancer Cells via PI3K/AKT and MAPK/ERK Pathways. Oncotarget, 8, 99901-99912. [Google Scholar] [CrossRef] [PubMed]
[9] Ong, C., Daemen, A., Oeh, J., et al. (2016) Breast Cancer Cell Lines with Acquired Resistance to Selective ERα Degraders (SERDs) Are Dependent on PI3K Signaling. Cancer Research, 76, 1803-1803.
[10] Huemer, F., Bartsch, R. and Gnant, M. (2014) The PI3K/AKT/MTOR Signaling Pathway: The Role of PI3K and AKT Inhibitors in Breast Cancer. Current Breast Cancer Reports, 6, 59-70. [Google Scholar] [CrossRef] 
[11] Arthur, J.S. and Ley, S.C. (2013) Mitogen-Activated Protein Kinases in Innate Immunity. Nature Reviews Immunology, 13, 679-692. [Google Scholar] [CrossRef] [PubMed]
[12] Kim, E.J. and Juhnn, Y.S. (2015) Cyclic AMP Signaling Reduces Sirtuin 6 Expression in Non-Small Cell Lung Cancer Cells by Promoting Ubiquitin-Proteasomal Degradation via Inhibition of the Raf-MEK-ERK (Raf/Mitogen-Activated Extracellular Signal-Regulated Kinase/Extracellular Signal-Regulated Kinase) Pathway. The Journal of Biological Chemistry, 290, 9604-9613. [Google Scholar] [CrossRef] 
[13] Wang, P.P., Luan, J.J., Xu, W.K., et al. (2017) Astragaloside IV Downregulates the Expression of MDR1 in Bel 7402/FU Human Hepatic Cancer Cells by Inhibiting the JNK/c-Jun/AP-1 Signaling Pathway. Molecular Medicine Reports, 16, 2761-2766. [Google Scholar] [CrossRef] [PubMed]
[14] 龙玲, 周琦, 张笠. p38MAPK 信号传导通路与卵巢癌关系研究进展[J]. 国际妇产科学杂志, 2017, 44(5): 494-498.
[15] Zhou, Z., Qiao, J.X., Shetty, A., et al. (2014) Regulation of Estrogen Receptor Signaling in Breast Carcinogenesis and Breast Cancer Therapy. Cellular & Molecular Life Sciences, 71, 1549-1549. [Google Scholar] [CrossRef] [PubMed]
[16] 杜璟, 张晓丽, 蒋丽娜. 雌、孕激素受体和表皮生长因子受体在乳腺癌中的表达及其临床意义[J]. 中国老年学杂志, 2014, 34(19): 5405-5407.
[17] 逄晓玲, 王一丁, 朱杰, 等. 乳腺癌ER相关内分泌耐药机制的研究进展[J]. 转化医学电子杂志, 2017, 4(9): 62-65.
[18] 余沈桐, 韦伊芳, 马勇政, 等. 乳腺癌内分泌治疗耐药相关机制的研究进展[J]. 现代肿瘤医学, 2014, 22(9): 2240-2244.
[19] Heckler, M.M., Thakor, H., Schafer, C.C., et al. (2014) ERK/MAPK Regulates ERRγ Expression, Transcriptional Activity and Receptor-Mediated Tamoxifen Resistance in ER+ Breast Cancer. FEBS Journal, 281, 2431-2442. [Google Scholar] [CrossRef] [PubMed]
[20] Shi, J.F., Yang, N., Ding, H.J., et al. (2014) ERα Directly Activated the MDR1 Transcription to Increase Paclitaxel-Resistance of ERα-Positive Breast Cancer Cells in Vitro and in Vivo. The International Journal of Biochemistry & Cell Biology, 53, 35-45. [Google Scholar] [CrossRef] [PubMed]
[21] Kazuyoshi, M., Satomi, T., Junko, M., et al. (2010) Estrogen-Mediated Post Transcriptional Down-Regulation of P-Glycoprotein in MDR1-Transduced Human Breast Cancer Cells. Cancer Science, 97, 1198-1204. [Google Scholar] [CrossRef] [PubMed]
[22] 郑小维, 陈思颖, 张蔚鹏, 等. 乳腺癌多药耐药机制及其逆转策略研究进展[J]. 中国药房, 2015, 26(20): 135-138.
[23] 谢亚琳, 梁继珍, 苏宁. 吉非替尼与厄洛替尼在EGFR基因敏感突变晚期NSCLC患者一线治疗中的疗效比较[J]. 南方医科大学学报, 2015, 35(3): 446-449.
[24] 夏雯, 王树森. 激素受体阳性乳腺癌靶向治疗进展[J]. 中国肿瘤临床, 2017,44(13): 635-639.
[25] 张圣村, 马敏, 徐丽丽. 阿帕替尼逆转P-gp转运体介导的乳腺癌化疗多药耐药性的作用及其机制[J]. 肿瘤防治研究, 2018, 45(4): 210-214.
[26] Zhang, X., Zhang, B., Liu, J., et al. (2015) Mechanisms of Gefitinib-Mediated Reversal of Tamoxifen Resistance in MCF-7 Breast Cancer Cells by Inducing ERα Re-Expression. Scientific Reports, 5, Article No. 7835. [Google Scholar] [CrossRef] [PubMed]
[27] Gee, J.M.W., Harper, M., Hurcheson, I., et al. (2003) The Antiepidermal Growth Factor Receptor Agent Gefitinib (ZD1839/Iressa) Improves Antihormone Response and Prevents Development of Resistance in Breast Cancer in Vitro. Endocrinology, 144, 5105-5017. [Google Scholar] [CrossRef] [PubMed]
[28] 赖艳, 温悦, 卢来春. 胡椒碱对乳腺癌阿霉素耐药细胞株MCF-7/ADM细胞的逆转作用[J]. 中国药业, 2014, 23(15): 23-24.
[29] Yuan, W.Q., Zhang, R.R., Wang, J., et al. (2016) Asclepiasterol, a Novel C21 Steroidal Glycoside Derived from Asclepias curassavica, Reverses Tumor Multidrug Resistance by Down-Regulating P-Glycoprotein Expression. Oncotarget, 7, 31466-31483. [Google Scholar] [CrossRef] [PubMed]
[30] 孙凯, 孙菊萍. 雷公藤红素逆转乳腺癌细胞对多柔比星的耐药性及机制研究[J]. 浙江中西医结合杂志, 2017, 27(3): 184-188.
[31] 袁婷婷, 张乃丹, 何勇静, 等. 天然药物中植物雌激素样化学成分的研究进展[J]. 中国中药杂志, 2014, 39(23): 4526-4531.
[32] Zhang, B., Zhang, X., Tang, B., et al. (2012) Investigation of Elemene-Induced Reversal of Tamoxifen Resistance in MCF-7 Cells through Oestrogen Receptor α (ERα) Re-Expression. Breast Cancer Research & Treatment, 136, 399-406. [Google Scholar] [CrossRef] [PubMed]
[33] 程曼, 何坤, 李晶, 等. 铁螯合剂通过抑制P-gp的表达促进乳腺癌化疗增敏[J]. 生物医学工程学进展, 2017, 38(3): 135-139.

为你推荐