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1.黑龙江中医药大学,哈尔滨 150040
2.黑龙江中医药大学 附属第一医院,哈尔滨 150040
朱晓娅,在读硕士,从事中西医结合治疗妇科肿瘤的临床研究,E-mail:zhuxiaoya1226@163.com
韩凤娟,教授,主任医师,博士生导师,从事中西医结合治疗妇科肿瘤的临床研究,E-mail:hanfengjuan2004@163.com
纸质出版日期:2022-09-20,
网络出版日期:2022-05-25,
收稿日期:2022-01-09,
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朱晓娅,丁丹妮,张成鑫等.中药单体调控宫颈癌细胞自噬的研究进展[J].中国实验方剂学杂志,2022,28(18):245-251.
ZHU Xiaoya,DING Danni,ZHANG Chengxin,et al.Chinese Medicine Monomers Regulate Autophagy of Cervical Cancer Cells: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):245-251.
朱晓娅,丁丹妮,张成鑫等.中药单体调控宫颈癌细胞自噬的研究进展[J].中国实验方剂学杂志,2022,28(18):245-251. DOI: 10.13422/j.cnki.syfjx.20221523.
ZHU Xiaoya,DING Danni,ZHANG Chengxin,et al.Chinese Medicine Monomers Regulate Autophagy of Cervical Cancer Cells: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(18):245-251. DOI: 10.13422/j.cnki.syfjx.20221523.
自噬是一种溶酶体介导的在细胞应激过程中捕获并降解功能障碍的细胞器及无用蛋白的分解过程,在宫颈癌中发挥双重作用。在宫颈癌早期阶段,自噬通过抑制致癌p62蛋白聚集体的积累,抑制其发生发展;宫颈癌进展到晚期,抑制癌细胞自噬可增强癌细胞对化疗药物的敏感性,抑制其增殖。近年来,中药单体调控自噬治疗宫颈癌的研究方兴未艾,受到国内外学者的广泛关注。其可通过多通路、多靶点调控宫颈癌细胞自噬,增加细胞凋亡率,减少癌细胞对化疗药物的耐药性。故笔者就中药单体通过自噬抑制宫颈癌的机制展开综述,以期为宫颈癌预防性及治疗性药物的发现发展寻求新突破。通过回顾文献发现在宫颈癌早期阶段,中药单体激活癌细胞自噬促进其凋亡,主要机制为增加溶酶体膜通透性(LMP)、增加化疗药敏感性、激活完整自噬流;宫颈癌进展到晚期,抑制癌细胞自噬减少其对化疗药物的敏感性,机制为抑制自噬小体及自溶酶体的形成。中药单体调节自噬治疗宫颈癌在体外实验取得了一定的效果,但临床实验研究较少,缺乏可靠的临床理论依据,因此开展更多的中药单体调节自噬治疗宫颈癌的临床实验研究以寻求治疗肿瘤更加可靠的理论依据是必不可少的。
Autophagy is a lysosome-mediated catabolic process that captures and degrades dysfunctional organelles and useless proteins during cellular stress process, which plays a dual role in cervical cancer. In the early stage of cervical cancer, autophagy inhibits the occurrence and development of cervical cancer by prohibiting the accumulation of oncogenic p62 protein. In the advanced stage of cervical cancer, inhibition of autophagy of cancer cells enhances the sensitivity of cancer cells to chemotherapeutic drugs, thus inhibiting their proliferation. In recent years, the research on Chinese medicine monomers regulating autophagy in the treatment of cervical cancer has attracted extensive attention from scholars at home and abroad. Chinese medicine monomers regulate the autophagy of cervical cancer cells through multiple pathways and multiple targets, so as to increase the apoptosis rate and reduce the resistance of cancer cells to chemotherapeutic drugs. Therefore, this paper reviewed the mechanism of Chinese medicine monomers in inhibiting cervical cancer through autophagy, expecting to find new breakthroughs in the discovery and development of preventive and therapeutic drugs for cervical cancer. By reviewing the literature, it was found that in the early stage of cervical cancer, Chinese medicine monomers activated autophagy to promote apoptosis of cancer cells, and the main mechanism was to increase lysosomal membrane permeability and chemotherapeutic sensitivity and activate intact autophagy flow. In the advanced stage of cervical cancer, inhibition of autophagy reduced the sensitivity of cancer cells to chemotherapy drugs by inhibiting the formation of autophagosomes and autolysosomes. The treatment of cervical cancer by Chinese medicine monomers regulating autophagy has achieved certain effect, but there are few clinical experimental studies and lack of reliable clinical theoretical basis. Therefore, it is essential to carry out more clinical experimental studies on Chinese medicine monomers regulating autophagy to treat cervical cancer, thus finding more reliable theoretical basis for the treatment of tumors.
宫颈癌中药单体细胞自噬抗癌作用研究进展
cervical cancerChinese medicine monomersautophagyanticancer effectresearch progress
赵琛,宋淑芳.我国宫颈癌流行病学及病因学的研究[J].医学信息,2021,34(5):6-8.
肖利平,岑苏.中药扶正解毒方联合重组人干扰素α-2b对年轻女性宫颈HPV感染的临床效果研究[J].中华中医药学刊,2021,39(12):248-250.
楼姣英,金哲,李云波.清毒栓血清药对宫颈癌SiHa细胞凋亡及周期的影响[J].北京中医药,2008(7):563-565.
冯蓓,冯艳,师晓艳.顺铂同步放疗联合扶正祛邪中药治疗中晚期宫颈癌的研究[J].现代中西医结合杂志,2019,28(20):2247-2249,2253.
吴露冰.中药及其单体治疗宫颈人乳头瘤病毒感染宫颈癌的研究进展[J].现代中西医结合杂志,2020,29(14):1593-1596.
MIZUSHIMA N, LEVINE B. Autophagy in human diseases[J]. N Engl J Med,2020,383(16):1564-1576.
YANG Y. Lysosomal dysfunction and autophagy blockade contribute to autophagy-related cancer suppressing peptide-induced cytotoxic death of cervical cancer cells through the AMPK/mTOR pathway[J]. J Exp Clin Cancer Res,2020,39(1):197.
NAGA C P, GURRAM L, CHOPRA S, et al. The management of locally advanced cervical cancer[J].Curr Opin Oncol,2018,30(5):323-329.
ORFANELLI T, JEONG J M, DOULAVERIS G, et al. Involvement of autophagy in cervical, endometrial and ovarian cancer[J]. Int J Cancer,2014,135(3):519-528.
KLIONSKY D J, BAEHRECKE E H, BRUMELL J H, et al. A comprehensive glossary of autophagy-related molecules and processes (2nd edition) [J].Autophagy,2011,7(11):1273-1294.
WEI F, JIANG X, GAO H Y, et al. Liquiritin induces apoptosis and autophagy in cisplatin (DDP)-resistant gastric cancer cells in vitro and xenograft nude mice in vivo[J]. Int J Oncol, 2017,51(5):1383-1394.
DIKIC I, ELAZAR Z. Mechanism and medical implications of mammalian autophagy[J].Nat Rev Mol Cell Biol,2018,19(6):349-364.
祁璘,张晓兰,琪美格,等.自噬标记蛋白Beclin1在宫颈癌组织中的表达检测及其与肿瘤增殖侵袭活性的关系[J].临床和实验医学杂志,2018,17(2):206-208.
HU Y F, LEI X, ZHANG H Y, et al. Expressions and clinical significance of autophagy-related markers Beclin1, LC3, and EGFR in human cervical squamous cell carcinoma[J].Onco Targets Ther, 2015, doi:10.2147/OTT.S86844http://dx.doi.org/10.2147/OTT.S86844.
SUN C Y, ZHANG Q Y, ZHENG G J, et al. Autophagy and its potent modulators from phytochemicals in cancer treatment[J]. Cancer Chemother Pharmacol,2019,83(1):17-26.
周冠琼,戴红艳,王昊珏,等.自噬相关蛋白p62、Beclin1在宫颈癌癌组织中的表达及意义[J].中国临床研究,2019,32(12):1685-1688.
LI X, HE S, MA B. Autophagy and autophagy-related proteins in cancer[J]. Mol Cancer,2020,19(1):12.
MA L, CHENG Y, ZENG J. MLK3 silence induces cervical cancer cell apoptosis via the Notch-1/autophagy network[J]. Clin Exp Pharmacol Physiol,2019,46(9):854-860.
TOWERS C G, WODETZKI D, THORBURN A. Autophagy and cancer: Modulation of cell death pathways and cancer cell adaptations[J]. J Cell Biol,2020,219(1):e201909033.
COOPE K F. Till death do us part: The marriage of autophagy and apoptosis[J].Oxid Med Cell Longev, 2018, doi:10.1155/2018/4701275http://dx.doi.org/10.1155/2018/4701275.
ZOU Y, SAREM M, XIANG S, et al. Autophagy inhibition enhances matrine derivative MASM induced apoptosis in cancer cells via a mechanism involving reactive oxygen species-mediated PI3K/Akt/mTOR and ERK/p38 signaling[J]. BMC Cancer,2019,19(1):949.
刘丽耘,吴永灿,肖玮,等.中医药调控自噬流的研究进展[J].中药药理与临床,2021,37(2):204-210.
PISTRITTO G, TRISCIUOGLIO D, CECI C, et al. Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies[J]. Aging,2016,8(4):603-619.
KIM Y C, GUAN K L. mTOR: A pharmacologic target for autophagy regulation[J]. J Clin Invest,2015,125(1):25-32.
XU Z, HAN X, OU D, et al. Targeting PI3K/Akt/mTOR-mediated autophagy for tumor therapy[J]. Appl Microbiol Biotechnol,2020,104(2):575-587.
JEYAMOHAN S, MOORTHY R K, KANNAN M K, et al. Parthenolide induces apoptosis and autophagy through the suppression of PI3K/Akt signaling pathway in cervical cancer[J]. Biotechnol Lett,2016,38(8):1251-1260.
刘莹莹,潘莹,申芳芳,等.蓝萼乙素对宫颈癌细胞迁移与侵袭影响作用机制[J].中华肿瘤防治杂志,2019,26(4):212-220.
PAN Y, BAI J, SHEN F, et al. Glaucocalyxin B induces apoptosis and autophagy in human cervical cancer cells[J].Mol Med Rep,2016,14(2):1751-1755.
李娜,张天栋,王月峰,等.雷公藤红素体内外诱导人宫颈癌HeLa细胞自噬作用及分子机制[J].中国药学杂志,2018,53(7):513-517.
LENG S, HAO Y, DU D, et al. Ursolic acid promotes cancer cell death by inducing Atg5-dependent autophagy[J].Int J Cancer,2013,133(12):2781-2790.
INOKI K, KIM J, GUAN K L. AMPK and mTOR in cellular energy homeostasis and drug targets[J]. Annu Rev Pharmacol Toxicol,2012, doi:10.1146/annurev-pharmtox-010611-134537http://dx.doi.org/10.1146/annurev-pharmtox-010611-134537.
YANG Y, WANG Q, SONG D, et al. Lysosomal dysfunction and autophagy blockade contribute to autophagy-related cancer suppressing peptide-induced cytotoxic death of cervical cancer cells through the AMPK/mTOR pathway[J]. J Exp Clin Cancer Res,2020,39(1):197.
ZHANG J. Crocin induces autophagic cell death and inhibits cell invasion of cervical cancer SiHa cells through activation of PI3K/Akt[J]. Ann Transl Med,2020,8(18):1180.
李菡,武康雄,史阔豪,等.土贝母化学成分、药理作用及临床应用研究进展[J].中国中药杂志,2021,46(17):4314-4322.
FENG X, ZHOU J, LI J, et al. Tubeimoside I induces accumulation of impaired autophagolysosome against cervical cancer cells by both initiating autophagy and inhibiting lysosomal function[J]. Cell Death Dis,2018,9(11):1117.
陈琼芳,王钢,李钊飞,等.吉马酮药理作用的研究进展[J].中华中医药学刊,2017,35(9):2312-2315.
姚宗花,张先娟,郭敬敬,等.吉马酮激活AMPK诱导宫颈癌HeLa细胞自噬和凋亡[J].中国免疫学杂志,2020,36(17):2105-2108,2114.
PARKW H, KIM S H. Involvement of reactive oxygen species and glutathione in gallic acid-induced human umbilical vein endothelial cell death[J]. Oncol Rep,2012,28(2):695-700.
孔翠翠,李艳兰,宫鹏超,等.蟾蜍灵诱导人宫颈癌C33A细胞自噬作用的机理研究[J].现代肿瘤医学,2019,27(24):4350-4354.
WANG L, LI J, SHI X, et al. Antimalarial Dihydroartemisinin triggers autophagy within HeLa cells of human cervical cancer through Bcl-2 phosphorylation at Ser70[J]. Phytomedicine, 2019, doi:10.1016/j.phymed.2018.09.221http://dx.doi.org/10.1016/j.phymed.2018.09.221.
贺靖澜,李宗虎,董晓辉,等.紫檀芪通过激活自噬缓解脊髓神经元细胞氧化应激损伤的作用及其机制[J].中国细胞生物学学报,2017,39(8):991-999.
钟桂兰,周知,王茹,等.紫檀芪对宫颈癌细胞自噬及SIRT1-FoxO信号通路的影响[J].中国病理生理杂志,2020,36(8):1439-1443.
WANG T, DING Y, YANG Y, et al. Synergistic antitumour effects of triptolide plus 10-hydroxycamptothecin onbladder cancer[J].Biomed Pharmacother, 2019, doi:10.1016/j.biopha.2019.108899http://dx.doi.org/10.1016/j.biopha.2019.108899.
陈干涛,董卫国.羟喜树碱通过诱导自噬抗宫颈癌的机制研究[J].实用癌症杂志,2017,32(3):349-353.
HSIN M C, HSIEH Y H, WANG P H, et al. Hispolon suppresses metastasis via autophagic degradation of cathepsin S in cervical cancer cells[J]. Cell Death Dis,2017,8(10):e3089.
WANG F, GÓMEZ-SINTES R, BOYA P. Lysosomal membrane permeabilization and cell death[J]. Traffic,2018,19(12):918-931.
HSU K F, WU C L, HUANG S C, et al. Cathepsin L mediates resveratrol-induced autophagy and apoptotic cell death in cervical cancer cells[J]. Autophagy,2009,5(4):451-460.
TRYBUS W, KRÓL T, TRYBUS E, et al. Changes in the lysosomal system of cervical cancer cells induced by emodin action[J].Anticancer Res,2017,37(11):6087-6096.
FENG Y, ZOU W, HU C, et al. Modulation of CASC2/miR-21/PTEN pathway sensitizes cervical cancer to cisplatin[J].Arch Biochem Biophys,2017, doi:10.1016/j.abb.2017.05.001http://dx.doi.org/10.1016/j.abb.2017.05.001.
SU J, ZHANG F, LI X, et al. Osthole promotes the suppressive effects of cisplatin on NRF2 expression to prevent drug-resistant cervical cancer progression[J]. Biochem Biophys Res Commun,2019,514(2):510-517.
LI Y J, LEI Y H, YAO N, et al. Autophagy and multidrug resistance in cancer[J]. Chin J Cancer,2017,36(1):52.
LIU Q, WANG C, MENG Q, et al. Puerarin sensitized K562/ADR cells by inhibiting NF-κB pathway and inducing autophagy[J].Phytother Res,2021,35(3):1658-1668.
李睿. 细胞周期蛋白Ⅰ(Cyclin Ⅰ)促进宫颈癌细胞产生顺铂耐药性的相关机制研究[D].郑州:郑州大学,2016.
陈璐,张娟,栾丽平.黄芩苷通过增强自噬介导顺铂对宫颈癌C-33A/cis细胞敏感性的影响[J].中药药理与临床, 2018,34(5):44-47.
王博,李恩萍,杨长春,等.汉黄岑素通过调节信号通路增强宫颈癌对顺铂的化疗敏感性[J].中国免疫学杂志, 2020,36(3):325-331.
翟秋丽,胡向丹,肖静,等.黄芪多糖可能通过调控细胞自噬提高宫颈癌HeLa细胞对顺铂的敏感性[J].中国中药杂志, 2018,43(4):805-812.
贾艳利,李军芳,梁高峰.柚皮素通过AMPK通路介导的自噬对顺铂耐药宫颈癌细胞(HeLa/DDP)顺铂耐药性的影响[J].现代药物与临床, 2021,36(5):878-884.
AKCAY A, NGUYEN Q, HE Z, et al. IL-33 exacerbates acute kidney injury[J]. J Am Soc Nephrol, 2011,22(11):2057-2067.
POTOČNJAK I, ŠIMIĆ L, VUKELIĆ I, et al. Oleanolic acid attenuates cisplatin-induced nephrotoxicity in mice and chemosensitizes human cervical cancer cells to cisplatin cytotoxicity[J]. Food Chem Toxicol,2019, doi:10.1016/j.fct.2019.110676http://dx.doi.org/10.1016/j.fct.2019.110676.
WANG Y, CHEN Y, CHEN X, et al. Angelicin inhibits the malignant behaviours of human cervical cancer potentially via inhibiting autophagy[J].Exp Ther Med,2019,18(5):3365-3374.
GAO J, YU H, GUO W, et al. The anticancer effects of ferulic acid is associated with induction of cell cycle arrest and autophagy in cervical cancer cells[J].Cancer Cell Int,2018, doi:10.1186/s12935-018-0595-yhttp://dx.doi.org/10.1186/s12935-018-0595-y.
牟丽云,邢翔飞,陈重旭,等.吉祥草活性成分RCE-4触发内质网应激调控人宫颈癌CaSki细胞周期阻滞[J].中国药理学通报,2021,37(9):1224-1231.
XIANG W, ZHANG R J, JIN G L, et al. RCE-4, a potential anti-cervical cancer drug isolated from Reineckia carnea, induces autophagy via the dual blockade of PI3K and ERK pathways in cervical cancer CaSki cells[J].Int J Mol Med,2020,45(1):245-254.
姜广利,马静静,何胜悦.双氢青蒿素通过调控细胞自噬性死亡增强宫颈癌细胞的化疗敏感性[J].中国免疫学杂志,2019,35(10):1213-1218.
卢文,杨艳梅,马敬全,等.自噬在熊果酸抑制人宫颈癌HeLa细胞增殖中的作用[J].中国肿瘤,2016,25(7):553-558.
SETTEMBRE C, FRALDI A, MEDINA D L, et al. Signals from the lysosome: A control centre for cellular clearance and energy metabolism[J].Nat Rev Mol Cell Biol,2013,14(5):283-296.
YANG Y, WANG Q, SONG D, et al. Lysosomal dysfunction and autophagy blockade contribute to autophagy-related cancer suppressing peptide-induced cytotoxic death of cervical cancer cells through the AMPK/mTOR pathway[J]. J Exp Clin Cancer Res,2020,39(1):197.
WANG J, BIAN S, WANG S, et al. Ginsenoside Rh2 represses autophagy to promote cervical cancer cell apoptosis during starvation[J].Chin Med,2020,15(1):118.
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