Advances in the study of chemotherapy resistance mechanisms in breast cancer based on genomics perspective
-
摘要: 乳腺癌(BC)于2020年首次成为全球患病率最高的癌症,是女性常见的癌症之一。乳腺癌作为一种生长迅速的浸润性癌症,严重威胁全球女性的健康。目前,乳腺癌的主要治疗手段为化学治疗,然而伴随着相关药物(主要包括紫杉醇、蒽环类和铂类)的使用,由于膜转运体、凋亡诱导与自噬诱导的化学抗性、DNA损伤修复能力增强、肿瘤微环境等因素出现了多药耐药问题。多药耐药(MDR)是导致乳腺癌患者预后差的重要原因之一。因此探索多药耐药相关的分子机制,找到对应的耐药关键基因一直是临床研究热点之一。已有很多研究表明,ATP结合盒转运蛋白(本文重点论述ABCB1、ABCC与ABCG2)、谷胱甘肽-S-转肽酶(GST-π)、拓扑异构酶Ⅱ(TOPO Ⅱ)、长非编码RNA(LncRNA)、含半胱氨酸的天冬氨酸蛋白水解酶3(CASP3)等基因与乳腺癌化疗耐药密切相关。本研究对乳腺癌化疗耐药基因相关的文献进行回顾和系统综述,并且基于现有耐药机制的相关研究,探讨应对乳腺癌化疗耐药的有效策略,为今后化疗耐药靶向治疗的研究提供一定的参考。Abstract: Breast cancer, which became the cancer with the highest prevalence rate in the world for the first time in 2020, is one of the most common cancers in women. As a fast-growing invasive cancer, breast cancer has become a serious threat to women ' s health worldwide. Currently, the mainstay of breast cancer treatment is chemotherapy, however, along with the use of related drugs (mainly including paclitaxel, anthracyclines, and platinums), the problem of multidrug resistance has arisen due to membrane transporters, apoptosis-induced and autophagy-induced chemoresistance, enhanced DNA damage repair, and the tumor microenvironment. Multidrug resistance is one of the major causes of poor prognosis in breast cancer patients. Therefore, exploring the molecular mechanisms related to multidrug resistance and finding the corresponding key genes for drug resistance has been one of the hotspots of clinical research. Many studies have shown that ATP-binding cassette transporter proteins (this article focuses on ABCB1, ABCC and ABCG2) are involved in multidrug resistance, glutathione-S-transferase (GST-π), topoisomerase Ⅱ (TOPO Ⅱ), long non-coding RNA (LncRNA) and cysteine-containing aspartic acid protein hydrolase 3 (CASP3) are genes closely associated with chemoresistance in breast cancer. In this study, we systematically reviewed the literature related to chemoresistance genes in breast cancer, and explored the effective strategies to deal with breast cancer chemoresistance based on the existing studies on the mechanism of chemoresistance, so as to provide some references for the research on chemoresistance-targeted therapies in the future.
-
Key words:
- Breast cancer /
- Genes /
- Drug resistance /
- Chemotherapy /
- Treatment
-
[1] SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3): 209-249. doi: 10.3322/caac.21660 [2] MOLLAZADEH S, SAHEBKAR A, HADIZADEH F, et al. Structural and functional aspects of P-glycoprotein and its inhibitors[J]. Life Sci, 2018, 214: 118-123. doi: 10.1016/j.lfs.2018.10.048 [3] SUI J H, HE M M, YANG Y D, et al. Reversing P-glycoprotein-associated multidrug resistance of breast cancer by targeted acid-cleavable polysaccharide nanoparticles with lapatinib sensitization[J]. ACS Appl Mater Interfaces, 2020, 12(46): 51198-51211. doi: 10.1021/acsami.0c13986 [4] GUESTINI F, ONO K, MIYASHITA M, et al. Impact of Topoisomerase Ⅱα, PTEN, ABCC1/MRP1, and KI67 on triple-negative breast cancer patients treated with neoadjuvant chemotherapy[J]. Breast Cancer Res Treat, 2019, 173(2): 275-288. doi: 10.1007/s10549-018-4985-6 [5] ZHANG H, ZHANG X Y, KANG X N, et al. LncRNA-SNHG7 enhances chemotherapy resistance and cell viability of breast cancer cells by regulating miR-186[J]. Cancer Manag Res, 2020, 12: 10163-10172. doi: 10.2147/CMAR.S270328 [6] 叶柳青, 丁金旺, 张敏, 等. 同源盒基因转录反义RNA(HOTAIR)在乳腺癌临床诊疗中的研究进展[J]. 中华全科医学, 2018, 16(2): 286-290. doi: 10.16766/j.cnki.issn.1674-4152.000080YE L Q, DING J W, ZHANG M, et al. Research progress of HOX transcript antisense RNA in clinical diagnosis and treatment of breast cancer[J]. Chinese Journal of General Practice, 2018, 16(2): 286-290. doi: 10.16766/j.cnki.issn.1674-4152.000080 [7] YIN Y M, XIN Y, ZHANG F, et al. Overcoming ABCB1-mediated multidrug resistance by transcription factor BHLHE40[J]. Neoplasia, 2023, 39: 100891. DOI: 10.1016/j.neo.2023.100891. [8] ZHANG L, LI Y D, HU C H, et al. CDK6-PI3K signaling axis is an efficient target for attenuating ABCB1/P-gp mediated multi-drug resistance (MDR) in cancer cells[J]. Mol Cancer, 2022, 21(1): 103. doi: 10.1186/s12943-022-01524-w [9] 柴冬亚. 重楼皂苷Ⅰ逆转人乳腺癌细胞耐药的作用及机制研究[D]. 昆明: 昆明医科大学, 2019.CHAI D Y. Reversal effect and mechanism of action of Polyphyllin I ondrug resistance of human breast cancer cells[D]. Kunming: Kunming Medical University, 2019. [10] JACKSON J, LEUNG D, BURT H. The use of ultrasound to increase the uptake and cytotoxicity of dual taxane and P-glycoprotein inhibitor loaded, solid core nanoparticles in drug resistant cells[J]. UltrasonIcs, 2020, 101: 106033. DOI: 10.1016/j.ultras.2019.106033. [11] NANAYAKKARA A K, FOLLIT C A, CHEN G, et al. Targeted inhibitors of P-glycoprotein increase chemotherapeutic-induced mortality of multidrug resistant tumor cells[J]. Sci Rep, 2018, 8(1): 967. doi: 10.1038/s41598-018-19325-x [12] ZHONG P, CHEN X H, GUO R S, et al. Folic acid-modified nanoerythrocyte for codelivery of paclitaxel and tariquidar to overcome breast cancer multidrug resistance[J]. Mol Pharm, 2020, 17(4): 1114-1126. doi: 10.1021/acs.molpharmaceut.9b01148 [13] MAKUCH-KOCKA A, KOCKI J, BRZOZOWSKA A, et al. Analysis of changes in the expression of selected genes from the ABC family in patients with triple-negative breast cancer[J]. Int J Mol Sci, 2023, 24(2): 1257. doi: 10.3390/ijms24021257 [14] TO K K W, WU X, YIN C, et al. Reversal of multidrug resistance by Marsdenia tenacissima and its main active ingredients polyoxypregnanes[J]. J Ethnopharmacol, 2017, 203: 110-119. doi: 10.1016/j.jep.2017.03.051 [15] 詹东梅. 南蛇藤素对胃癌顺铂耐药SGC7901/DDP细胞的抑制作用及机制研究[D]. 扬州: 扬州大学, 2021.ZHAN D M. Inhibitory effect of celastrol on cisplatin resistant gastric cancer SGC7901/DDP cells and its mechanism[D]. Yangzhou: Yangzhou University, 2021. [16] CHEN Y, ZHOU H Y, YANG S F, et al. Increased ABCC2 expression predicts cisplatin resistance in non-small cell lung cancer[J]. Cell Biochem Funct, 2021, 39(2): 277-286. doi: 10.1002/cbf.3577 [17] CUI J H, JIA J P. Natural COX-2 inhibitors as promising anti-inflammatory agents: an update[J]. Curr Med Chem, 2021, 28(18): 3622-3646. doi: 10.2174/0929867327999200917150939 [18] AJIYH A K, SUBRAMANI S, MANICKAM A H, et al. Chemotherapeutic resistance genes of breast cancer patients-an overview[J]. Adv Pharm Bull, 2022, 12(4): 649-657. [19] ZHANG Y S, YANG C, HAN L, et al. Expression of BCRP/ABCG2 protein in invasive breast cancer and response to neoadjuvant chemotherapy[J]. Oncol Res Treat, 2022, 45(3): 94-101. doi: 10.1159/000520871 [20] FAN Y F, ZHANG W, ZENG L L, et al. Dacomitinib antagonizes multidrug resistance (MDR) in cancer cells by inhibiting the efflux activity of ABCB1 and ABCG2 transporters[J]. Cancer Lett, 2018, 421: 186-198. doi: 10.1016/j.canlet.2018.01.021 [21] JI N, YANG Y Q, CAI C Y, et al. Selonsertib (GS-4997), an ASK1 inhibitor, antagonizes multidrug resistance in ABCB1-and ABCG2-overexpressing cancer cells[J]. Cancer Lett, 2019, 440: 82-93. [22] GUPTA P, ZHANG Y K, ZHANG X Y, et al. Voruciclib, a potent CDK4/6 inhibitor, antagonizes ABCB1 and ABCG2-mediated multi-drug resistance in cancer cells[J]. Cell Physiol Biochem, 2018, 45(4): 1515-1528. doi: 10.1159/000487578 [23] BUKOWSKI K, KCIUK M, KONTEK R. Mechanisms of multidrug resistance in cancer chemotherapy[J]. Int J Mol Sci, 2020, 21(9): 3233. doi: 10.3390/ijms21093233 [24] DE LUCA A, PARKER L J, ANG W H, et al. A structure-based mechanism of cisplatin resistance mediated by glutathione transferase P1-1[J]. Proc Natl Acad Sci U S A, 2019, 116(28): 13943-13951. doi: 10.1073/pnas.1903297116 [25] 王亚琪, 曾普华, 郜文辉, 等. 益气化瘀解毒方对MRP、GST-π和Topo Ⅱ基因在Sorafenib获得性耐药人肝癌QGY7702细胞表达的干预研究[J]. 吉林中医药, 2020, 40(4): 505-509.WANG Y Q, ZENG P H, GAO W H, et al. Intervention study of Yiqi Huayu Jiedu Prescription on the expression of MRP, GST-π and Topo Ⅱ genes in sorafenib acquired resistant human hepatocellular carcinoma QGY7702 cells[J]. Jilin Journal of Chinese Medicine, 2020, 40(4): 505-509. [26] LAU T Y, KWAN H Y. Fucoxanthin is a potential therapeutic agent for the treatment of breast cancer[J]. Mar Drugs, 2022, 20(6): 370. doi: 10.3390/md20060370 [27] EID S Y, ALTHUBITI M A, ABDALLAH M E, et al. The carotenoid fucoxanthin can sensitize multidrug resistant cancer cells to doxorubicin via induction of apoptosis, inhibition of multidrug resistance proteins and metabolic enzymes[J]. Phytomedicine, 2020, 77: 153280. DOI: 10.1016/j.phymed.2020.153280. [28] MCKIE S J, NEUMAN K C, MAXWELL A. DNA topoisomerases: advances in understanding of cellular roles and multi-protein complexes via structure-function analysis[J]. Bioessays, 2021, 43(4): e2000286. DOI: 10.1002/bies.202000286. [29] SUNDOV D, MISE B P, MRKLIC I, et al. Prognostic significance of MAPK, Topo Ⅱα and E-cadherin immunoexpression in ovarian serous carcinomas[J]. Neoplasma, 2017, 64(2): 289-298. doi: 10.4149/neo_2017_217 [30] MANVILLE C M, SMITH K, SONDKA Z, et al. Genome-wide ChIP-seq analysis of human TOP2B occupancy in MCF7 breast cancer epithelial cells[J]. Open Biol, 2015, 4(11): 1436-1447. doi: 10.1242/bio.014308 [31] MATIAS-BARRIOS V M, RADAEVA M, SONG Y, et al. Discovery of new catalytic topoisomerase Ⅱ inhibitors for anticancer therapeutics[J]. Front Oncol, 2021, 10: 633142. DOI: 10.3389/fonc.2020.633142. [32] 沙新海, 邢广琳, 黄强. 补骨脂素对乳腺癌干细胞的毒性作用及Topo Ⅱ α基因mRNA和蛋白表达水平的影响[J]. 临床和实验医学杂志, 2019, 18(22): 2397-2400. doi: 10.3969/j.issn.1671-4695.2019.22.012SHA X H, XING G L, HUANG Q. Toxic effects of psoralen on breast cancer stem cells and its influence on TopoⅡα gene m RNA and protein expression level[J]. Journal of Clinical and Experimental Medicine, 2019, 18(22): 2397-2400. doi: 10.3969/j.issn.1671-4695.2019.22.012 [33] CAI P F, OTTEN A B C, CHENG B B, et al. A genome-wide long noncoding RNA CRISPRi screen identifies PRANCR as a novel regulator of epidermal homeostasis[J]. Genome Res, 2020, 30(1): 22-34. doi: 10.1101/gr.251561.119 [34] HUANG Q Y, LIU G F, QIAN X L, et al. Long non-coding RNA: dual effects on breast cancer metastasis and clinical applications[J]. Cancers(Basel), 2019, 11(11): 1802. [35] QIAO Y, WANG B, YAN Y, et al. Long noncoding RNA ST8SIA6-AS1 promotes cell proliferation and metastasis in triple-negative breast cancer by targeting miR-145-5p/CDCA3 to inactivate the p53/p21 signaling pathway[J]. Environ Toxicol, 2022, 37(10): 2398-2411. doi: 10.1002/tox.23605 [36] ZHANG X H, LI F Y, ZHOU Y D, et al. Long noncoding RNA AFAP1-AS1 promotes tumor progression and invasion by regulating the miR-2110/Sp1 axis in triple-negative breast cancer[J]. Cell Death Dis, 2021, 12(7): 627. doi: 10.1038/s41419-021-03917-z [37] WU J J, XU W, MA L N, et al. Formononetin relieves the facilitating effect of lncRNA AFAP1-AS1-miR-195/miR-545 axis on progression and chemo-resistance of triple-negative breast cancer[J]. Aging (Albany NY), 2021, 13(14): 18191-18222. [38] 张娜娜. Caspase-3和Bcl-2表达与乳腺癌细胞凋亡及其临床病理特征的相关性分析[J]. 实用癌症杂志, 2021, 36(10): 1609-1613. doi: 10.3969/j.issn.1001-5930.2021.10.011ZHANG N N. Correlation analysis of Caspase-3 and Bcl-2 expression with breast cancer cell apoptosis and its clinicopathological characteristics[J]. The Practical Journal of Cancer, 2021, 36(10): 1609-1613. doi: 10.3969/j.issn.1001-5930.2021.10.011 [39] 杨春梅, 崔晓博, 罗强, 等. 姜黄素逆转耐药作用与Caspase-3关系研究[J]. 实用医学杂志, 2012, 28(3): 355-357. doi: 10.3969/j.issn.1006-5725.2012.03.005YANG C M, CUI X B, LUO Q, et al. Relationship between curcumin resistance reversal and Caspase-3[J]. The Journal of Practical Medicine, 2012, 28(3): 355-357. doi: 10.3969/j.issn.1006-5725.2012.03.005
点击查看大图
计量
- 文章访问数: 297
- HTML全文浏览量: 77
- PDF下载量: 38
- 被引次数: 0