

浏览全部资源
扫码关注微信
1.广西中医药大学,南宁 530200
2.广西中医药大学 壮瑶药重点实验室,南宁 530200
Received:18 October 2021,
Published Online:27 December 2021,
Published:05 May 2022
移动端阅览
林思,秦慧真,邓玲玉等.紫草素抗肿瘤作用研究进展[J].中国实验方剂学杂志,2022,28(09):273-282.
LIN Si,QIN Hui-zhen,DENG Ling-yu,et al.Anti-tumor Effect of Shikonin: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(09):273-282.
林思,秦慧真,邓玲玉等.紫草素抗肿瘤作用研究进展[J].中国实验方剂学杂志,2022,28(09):273-282. DOI: 10.13422/j.cnki.syfjx.20220524.
LIN Si,QIN Hui-zhen,DENG Ling-yu,et al.Anti-tumor Effect of Shikonin: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(09):273-282. DOI: 10.13422/j.cnki.syfjx.20220524.
癌症的发病率与死亡率逐年递增,严重威胁人类健康。目前,以化疗为主治疗癌症的方法虽能延长患者的生存时间,但其严重的不良反应往往使患者预后不良。故寻找高效低毒的抗癌药物已成为全世界临床共同关注的焦点。中药有效成分,具有不良反应小、多靶点调控等优势,其抗肿瘤活性受到广大科研者的热爱。紫草素为萘醌类化合物,是紫草的主要有效成分之一,具有抗肿瘤、抗炎、抗氧化等药理作用。研究表明,紫草素对多种肿瘤细胞显示出显著的抗肿瘤活性,能够抑制乳腺癌、肺癌、肝癌、宫颈癌、卵巢癌、结肠癌、前列腺癌等多种癌症的发生发展。紫草素抗肿瘤机制主要是通过多途径、多靶点抑制肿瘤细胞增殖,促进活性氧(ROS)生成,诱导肿瘤细胞发生凋亡,阻滞细胞周期,诱导肿瘤细胞自噬,抑制肿瘤细胞迁移与侵袭等。此外,紫草素还能增加肿瘤细胞对抗肿瘤药物的敏感性,逆转肿瘤细胞耐药性。紫草素抗肿瘤作用涉及的信号通路有磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt),PI3K/Akt/哺乳动物雷帕霉素靶蛋白(mTOR),丝裂原活化蛋白激酶(MAPK),丙酮酸激酶同工酶M2/信号传导与转录激活因子3(PKM2/STAT3),Kelch样环氧氯丙烷相关蛋白1/核因子E
2
相关因子2(Keap1/Nrf2)等,但主要通过调控PI3K/Akt信号通路发挥抗肿瘤作用。笔者查阅国内外关于紫草素抗肿瘤作用及机制的相关文献,对其近3年的相关研究进行归纳总结,为紫草素的抗肿瘤作用进一步深入研究及抗肿瘤药物的新药研发提供相应参考。
The incidence and mortality of cancer are increasing year by year, seriously threatening human health. At present, the chemotherapy-based treatment of cancer can prolong the survival time of patients, but its severe side effects and adverse reactions often lead to poor prognosis. Therefore, searching for anti-cancer drugs with high efficiency and low toxicity has become the focus of clinical attention from all over the world. The effective components of Chinese medicine have the advantages of mild side effect and multi-target regulation, and their anti-tumor activities are highly favored by many researchers. Shikonin, a naphthoquinone compound, is the main effective component of Arnebiae Radix, with anti-tumor, anti-inflammatory, antioxidant, and other pharmacological effect. Studies have shown that shikonin possesses significant anti-tumor activities against a variety of tumor cells, and it can inhibit the development of many cancers, such as breast cancer, lung cancer, liver cancer, cervical cancer, ovarian cancer, colon cancer, and prostate cancer. The anti-tumor mechanism of shikonin is mainly related to multi-pathway and multi-target inhibition of tumor cell proliferation, the promotion of reactive oxygen species (ROS) production, induction of tumor cell apoptosis, cell cycle arrest, and tumor cell autophagy, and the inhibition of tumor cell migration and invasion. In addition, shikonin can increase the sensitivity of tumor cells to anti-tumor drugs and reverse the drug resistance of tumor cells. The signaling pathways involved in the anti-tumor effect of shikonin include phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), PI3K/Akt/mammalian target of rapamycin (mTOR), mitogen-activated protein kinase (MAPK), pyruvate kinase M2/signal transducer and activator of transcription protein 3 (PKM2/STAT3), and Kelch-like epichlorohydrin-related protein 1/nuclear factor E
2
-related factor 2 (Keap1/Nrf2). The anti-tumor effects are mainly achieved through the regulation of the PI3K/Akt signaling pathway. Based on the relevant literature on the anti-tumor effect and mechanism of shikonin in China and abroad, the present study reviewed the research progress in the past three years to provide useful references for the further study of the anti-tumor effect of shikonin and the research and development of new antineoplastic drugs.
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 .
高文雅 , 张盟 , 陶仕英 , 等 . 基于网络药理学研究紫草抗乳腺癌的作用机制并对紫草素在MDA-MB-231细胞中进行验证 [J]. 中国临床药理学杂志 , 2021 , 37 ( 15 ): 2030 - 2034 .
闫伟平 , 谢法红 , 郭瑞杰 , 等 . 紫草素诱导三阴性乳腺癌细胞MDA-MB-231坏死性凋亡的作用及其机制 [J]. 山西医科大学学报 , 2021 , 52 ( 3 ): 249 - 254 .
黄静山 , 张洪岩 , 鲁继斌 . 紫草素诱导非小细胞肺癌A549细胞程序性坏死的实验研究 [J]. 临床肿瘤学杂志 , 2021 , 26 ( 6 ): 488 - 492 .
冯伟 , 马建文 , 饶梅冬 . 紫草素诱导卵巢癌SKOV3和A2780细胞坏死性凋亡的作用及其机制研究 [J]. 中国药业 , 2019 , 28 ( 1 ): 19 - 23 .
闫懋莎 , 杨燕芬 , 龚菊 , 等 . 紫草素通过下调HPV E6/E7蛋白表达抑制宫颈癌Caski细胞增殖 [J]. 基因组学与应用生物学 , 2020 , 39 ( 4 ): 1819 - 1823 .
蒋汉霞 , 刘志杰 . 紫草素调控PTEN/Akt通路抑制宫颈癌细胞增殖、侵袭研究 [J]. 热带医学杂志 , 2019 , 19 ( 7 ): 822 - 826,942 .
王洁 , 何振兴 , 赵菊花 , 等 . 紫草素对皮肤鳞状细胞癌细胞生长及PI3K/Akt信号通路的影响 [J]. 郑州大学学报:医学版 , 2019 , 54 ( 3 ): 414 - 418 .
王瑜 , 何施燕 , 朱若婷 , 等 . 紫草素对肝癌细胞SMMC-7721凋亡的影响及其机制 [J]. 中国应用生理学杂志 , 2021 , 37 ( 4 ): 415 - 418 .
刘长青 , 陈勇 , 谢冰帆 , 等 . 紫草素调控PI3K/Akt/mTOR信号通路影响人子宫内膜癌细胞株RL95-2增殖、凋亡的实验研究 [J]. 中国生育健康杂志 , 2019 , 30 ( 6 ): 571 - 575,601 .
雷喜锋 , 刘韬 , 董山潮 , 等 . 紫草素体外对人结肠癌生长抑制的作用 [J]. 昆明医科大学学报 , 2019 , 40 ( 7 ): 19 - 24 .
王元英 , 黎宝仁 , 符湘茹 , 等 . 紫草素对鼻咽癌CNE-2细胞增殖和侵袭的影响 [J]. 中国临床药理学杂志 , 2020 , 36 ( 16 ): 2459 - 2462 .
袁建华 , 杨亚运 , 王蕊 . 紫草素通过调控PI3K/Akt信号通路对卵巢癌HO-8910细胞周期及凋亡的影响 [J]. 中华生物医学工程杂志 , 2019 ( 2 ): 189 - 194 .
刘晓莉 , 姚草原 , 熊弢 . 紫草素对人非小细胞肺癌A549细胞增殖与凋亡的影响 [J]. 临床和实验医学杂志 , 2019 , 18 ( 19 ): 2052 - 2056 .
孙艳华 , 李明 , 徐建立 , 等 . 紫草素通过激活活性氧自由基诱导大肠癌细胞的凋亡 [J]. 世界中医药 , 2021 , 16 ( 15 ): 2316 - 2321 .
SHILNIKOVA K , PIAO J , KANG A , et al . Natural compound shikonin induces apoptosis and attenuates epithelial to mesenchymal transition in radiation-resistant human colon cancer cells [J]. Biomol Ther , 2021 , doi: 10.4062/biomolther.2021.088 http://dx.doi.org/10.4062/biomolther.2021.088 .
ALAM M M , KARIYA R , BOONNATE P , et al . Induction of apoptosis by Shikonin through ROS-mediated intrinsic and extrinsic apoptotic pathways in primary effusion lymphoma [J]. Transl Oncol , 2021 , 14 ( 3 ): 101006 .
LIU T C , SUN X , CAO Z W . Shikonin-induced necroptosis in nasopharyngeal carcinoma cells via ROS overproduction and upregulation of RIPK1/RIPK3/MLKL expression [J]. Oncotargets Ther , 2019 , 12 : 2605 - 2614 .
董莹莹 , 李威 . 紫草素对子宫内膜癌lshikawa细胞生物学行为的影响及可能机制 [J]. 解剖科学进展 , 2021 , 27 ( 1 ): 39 - 41 .
沃奇军 , 项飞 , 张大宏 . 紫草素对肾透明细胞癌抗凋亡作用与机制研究 [J]. 浙江中西医结合杂志 , 2021 , 31 ( 2 ): 116 - 120 .
LEE J H , HAN S H , KIM M , et al . Shikonin inhibits proliferation of melanoma cells by MAPK pathway-mediated induction of apoptosis [J]. Biosci Rep , 2021 , 41 ( 1 ): BSR20203834 .
LIU C , XUAN L Q , LI K , et al . Shikonin Inhibits Cholangiocarcinoma Cell Line QBC939 by Regulating Apoptosis,Proliferation,and Invasion [J]. Cell Transplant , 2021 , doi: 10.1177/0963689720979162 http://dx.doi.org/10.1177/0963689720979162 .
MA X , YU M , HAO C , et al . Shikonin induces tumor apoptosis in glioma cells via endoplasmic reticulum stress, and Bax/Bak mediated mitochondrial outer membrane permeability [J]. J Ethnopharmacol , 2020 , doi: 10.1016/j.jep.2020.113059 http://dx.doi.org/10.1016/j.jep.2020.113059 .
黎阳成 , 朱雪莲 , 贺志军 . 子宫内膜癌患者HE4、CA125水平变化及其临床意义 [J]. 检验医学与临床 , 2019 , 16 ( 4 ): 474 - 477,481 .
ZHANG Q Q , LIU Q , ZHENG S T , et al . Shikonin inhibits tumor growth of ESCC by suppressing PKM2 mediated aerobic glycolysis and STAT3 phosphorylation [J]. J Cancer , 2021 , 12 ( 16 ): 4830 - 4840 .
LIU T , LI S N , WU L W , et al . Experimental study of hepatocellular carcinoma treatment by shikonin through regulating PKM2 [J]. J Hepatocell Carcino , 2020 , doi: 10.2147/JHC.S237614 http://dx.doi.org/10.2147/JHC.S237614 .
马秀娟 , 朱婷 , 范洋 . 紫草素调节有氧糖酵解代谢诱导急性淋巴细胞白血病细胞凋亡 [J]. 现代肿瘤医学 , 2020 , 28 ( 10 ): 1620 - 1624 .
宋厦 , 高旋 , 韩秋玥 , 等 . 紫草素对人膀胱癌T24细胞增殖、凋亡、迁移与侵袭的影响 [J]. 解剖科学进展 , 2020 , 26 ( 2 ): 182 - 184,188 .
安兴晨 , 董天睿 , 王晶 , 等 . 紫草素诱导人乳腺癌MCF-7细胞凋亡及其机制探讨 [J]. 中国医刊 , 2019 , 54 ( 11 ): 1223 - 1226 .
崔忆旋 , 赵报 , 李佳会 , 等 . 紫草素通过上调RIP1、RIP3蛋白诱导下咽癌细胞发生坏死性凋亡 [J]. 山西医科大学学报 , 2019 , 50 ( 11 ): 1527 - 1530 .
MARKOWITSCH S D , JUETTER K M , SCHUPP P , et al . Shikonin reduces growth of docetaxel-resistant prostate cancer cells mainly through necroptosis [J]. Cancers , 2021 , 13 ( 4 ): 882 .
赵莉 , 黄景荣 , 龚承先 , 等 . 紫草素对人食管癌TE-1细胞增殖、凋亡和细胞周期的影响及其可能的机制 [J]. 中国肿瘤生物治疗杂志 , 2020 , 27 ( 8 ): 889 - 894 .
窦晓静 , 殷嘉 , 宋惠菁 , 等 . 紫草素对人胃癌细胞增殖和细胞周期的影响 [J]. 中国临床药理学杂志 , 2020 , 36 ( 20 ): 3272 - 3275 .
LIU Y , KANG X , NIU G , et al . Shikonin induces apoptosis and prosurvival autophagy in human melanoma A375 cells via ROS-mediated ER stress and p38 pathways [J]. Artif Cells Nanomed Biotechnol , 2019 , 47 ( 1 ): 626 - 635 .
AIELLO N M , KANG Y . Context-dependent EMT programs in cancer metastasis [J]. J Exp Med . 2019 , 216 ( 5 ): 1016 - 1026 .
李世玲 , 漆毅 , 袁晓安 , 等 . 紫草素对非小细胞肺癌细胞增殖和迁移的影响 [J]. 中国临床药理学杂志 , 2021 , 37 ( 16 ): 2152 - 2154 .
SHA L Y , LV Z Q , LIU Y J , et al . Shikonin inhibits the Warburg effect,cell proliferation,invasion and migration by downregulating PFKFB2 expression in lung cancer [J]. Mol Med Rep , 2021 , 24 ( 2 ): 1 - 10 .
PAN T , ZHANG F , LI F K , et al . Shikonin blocks human lung adenocarcinoma cell migration and invasion in the inflammatory microenvironment via the IL-6/STAT3 signaling pathway [J]. Oncol Rep , 2020 , 44 ( 3 ): 1049 - 1063 .
何刚 , 黄曦文 , 伍春莲 . 紫草素通过CD54和整合素抑制人肺癌H292细胞转移 [J]. 西华师范大学学报:自然科学版 , 2020 , 41 ( 3 ): 235 - 241 .
张小方 , 赵影 , 李琦 . 紫草素抑制非小细胞肺癌A549侵袭和迁移能力 [J]. 中国免疫学杂志 , 2019 , 35 ( 2 ): 197 - 201 .
徐洋 , 李硕 , 阴佳明 , 等 . 紫草素通过抑制STAT3-MMP2信号通路抑制胃癌MGC803细胞的迁移能力 [J]. 中国医院药学杂志 , 2021 , 41 ( 17 ): 1718 - 1722 .
邓秋媛 , 刘志坤 , 乔静 . 紫草素调控PKM2/STAT3信号通路抑制RBE细胞转移的研究 [J]. 毒理学杂志 , 2020 , 34 ( 5 ): 385 - 388 .
ZHANG J J , ZHOU J C , XIAO S F . Shikonin inhibits growth,invasion and glycolysis of nasopharyngeal carcinoma cells through inactivating the phosphatidylinositol 3 kinase/Akt signal pathway [J]. Anti-Cancer Drug 2020 , 31 ( 9 ): 932 - 941 .
LI X J , ZENG X P . Shikonin suppresses progression and epithelial-mesenchymal transition in hepatocellular carcinoma (HCC) cells by modulating miR-106b/SMAD7/TGF- β signaling pathway [J]. Cell Biol Int , 2020 , 44 ( 2 ): 467 - 476 .
LIU B , JIN J B , ZHANG Z Y , et al . Shikonin exerts antitumor activity by causing mitochondrial dysfunction in hepatocellular carcinoma through PKM2-AMPK-PGC1 α signaling pathway [J]. Biochem Cell Biol , 2019 , 97 ( 4 ): 397 - 405 .
史记 , 张烨 , 孙佩欣 , 等 . 紫杉醇联合紫草素对U87脑胶质瘤细胞的作用及机制初探 [J]. 现代肿瘤医学 , 2020 , 28 ( 5 ): 691 - 698 .
YUAN X , WU J , GUO X , et al . Autophagy in Acute Pancreatitis: Organelle Interaction and microRNA Regulation [J]. Oxid Med Cell Longev , 2021 , doi: 10.1155/2021/8811935 http://dx.doi.org/10.1155/2021/8811935 .
MULHOLLAND E J , GREEN W P , BUCKLEY N E , et al . Exploring the potential of microRNA Let-7c as a therapeutic for prostate cancer [J]. Mol Ther Nucleic Acids , 2019 , doi: 10.1016/j.omtn.2019.09.031 http://dx.doi.org/10.1016/j.omtn.2019.09.031 .
文蓉 , 李树玺 . 紫草素影响Let-7c的表达调控宫颈癌细胞C-33A生物学特性的研究 [J]. 国际检验医学杂志 , 2019 , 40 ( 23 ): 2822 - 2826,2831 .
CHEN Y , CHEN Z Y , CHEN L , et al . Shikonin inhibits triple-negative breast cancer-cell metastasis by reversing the epithelial-to-mesenchymal transition via glycogen synthase kinase 3 β -regulated suppression of β -catenin signaling [J]. Biochem Pharmacol , 2019 , doi: 10.1016/j.bcp.2019.05.001 http://dx.doi.org/10.1016/j.bcp.2019.05.001 .
IVAN D . Proteasomal and Autophagic Degradation Systems [J]. Annu Rev Biochem , 2017 , doi: 10.1146/annurev-biochem-061516-044908 http://dx.doi.org/10.1146/annurev-biochem-061516-044908 .
孙艳华 , 李明 , 徐建立 , 等 . 紫草素通过激活自噬相关的E1连接酶7信号通路诱导结肠癌细胞自噬 [J]. 安徽医药 , 2020 , 24 ( 12 ): 2336 - 2342,2545 .
XUAN F , JIAN J . Epigallocatechin gallate exerts protective effects against myocardial ischemia/reperfusion injury through the PI3K/Akt pathway-mediated inhibition of apoptosis and the restoration of the autophagic flux [J]. Int J Mol Med , 2016 , 38 ( 1 ): 328 - 336 .
MENG Q , DU X , WANG H , et al . Astragalus polysaccharides inhibits cell growth and pro-inflammatory response in IL-1 β -stimulated fibroblast-like synoviocytes by enhancement of autophagy via PI3K/Akt/mTOR inhibition [J]. Apoptosis , 2017 , 22 ( 9 ): 1138 - 1146 .
LU N , LI X , TAN R , et al . HIF-1 α /Beclin1-mediated autophagy is involved in neuroprotection induced by hypoxic preconditioning [J]. J Mol Neurosci , 2018 , 66 ( 2 ): 238 - 250 .
DU X , LIU B , LUAN X , et al . miR-30 decreases multidrug resistance in human gastric cancer cells by modulating cell autophagy [J]. Exp Ther Med , 2018 , 15 ( 1 ): 599 - 605 .
王书惠 , 尹秀艳 , 刘海英 , 等 . 紫草素通过PI3K/Akt/mTOR信号通路诱导人宫颈癌HeLa细胞凋亡和自噬 [J]. 中国病理生理杂志 , 2019 , 35 ( 7 ): 1189 - 1194 .
王军 , 杨雅娟 , 刘海涛 , 等 . 紫草素抑制PI3K/Akt/mTOR信号通路诱导人结肠癌SW480细胞凋亡和自噬的作用研究 [J]. 药物评价研究 , 2021 , 44 ( 2 ): 338 - 343 .
马艳华 , 黄芬 , 王文尖 . 紫草素对HepG2细胞增殖、凋亡和PI3K/Akt/NF- κ B信号通路蛋白表达的影响 [J]. 实用肝脏病杂志 , 2020 , 23 ( 4 ): 471 - 475 .
邵鑫 , 蒋先虹 , 王瑞 , 等 . 紫草素对人结肠癌细胞HCT116自噬和凋亡的影响 [J]. 中国药房 , 2021 , 32 ( 1 ): 51 - 55 .
ZHANG N , PENG F , WANG Y J , et al . Shikonin induces colorectal carcinoma cells apoptosis and autophagy by targeting galectin-1/JNK signaling axis [J]. Int J Biol Sci , 2020 , 16 ( 1 ): 147 - 161 .
姚越 , 张冲 , 韩兵 , 等 . 紫草素通过抑制人睾丸癌1-10和精原细胞瘤TCAM-2糖酵解诱导细胞死亡 [J]. 南方医科大学学报 , 2020 , 40 ( 9 ): 1288 - 1294 .
DALLAVALLE S , DOBRICIC V , LAZZARATO L , et al . Improvement of conventional anti-cancer drugs as new tools against multidrug resistant tumors [J]. Drug Resist Updat , 2020 , 50 ( 16 ): 100682 .
王孝锦 , 徐湛翔 . 抗肿瘤药物多药耐药机制的研究进展 [J]. 牡丹江医学院学报 , 2021 , 42 ( 3 ): 164 - 167 .
WANG L , STADLBAUER B , LYU C , et al . Shikonin enhances the antitumor effect of cabazitaxel in prostate cancer stem cells and reverses cabazitaxel resistance by inhibiting ABCG2 and ALDH3A1 [J]. Am J Cancer Res , 2020 , 10 ( 11 ): 3784 - 3800 .
张辉 , 张爽 , 刘扬帆 , 等 . 基于Keap1/Nrf2通路介导的自噬探讨紫草素对膀胱上皮癌BUC细胞化疗敏感性的影响 [J]. 中草药 , 2021 , 52 ( 12 ): 3642 - 3648 .
DU W Z , HAO X H , YUAN Z L , et al . Shikonin potentiates paclitaxel antitumor efficacy in esophageal cancercells via the apoptotic pathway [J]. Oncol Lett , 2019 , 18 ( 3 ): 3195 - 3201 .
路京 , 陈子龙 , 闵朕 , 等 . 紫草素逆转由肝细胞生长因子诱导的肺癌吉非替尼耐药 [J]. 中国病理生理杂志 , 2019 , 35 ( 1 ): 62 - 67 .
ZANG F R , RAO Y Q , ZHU X H , et al . Shikonin suppresses NEAT1 and Akt signaling in treating paclitaxel-resistant non-small cell of lung cancer [J]. Mol Med , 2020 , 26 ( 1 ): 28 - 28 .
刘亚楠 , 王炳先 , 路臣桂 , 等 . 紫草素对子宫内膜癌细胞增殖、凋亡和顺铂耐药性的影响 [J]. 中成药 , 2021 , 43 ( 8 ): 2219 - 2224 .
孙艳华 , 徐建立 , 李明 , 等 . 紫草素对人大肠癌HT29细胞化疗增敏作用研究 [J]. 中医学报 , 2021 , 36 ( 2 ): 361 - 365 .
樊涛 , 郭彦伟 , 任金山 , 等 . 紫草素对卵巢癌细胞株SKOV3放疗敏感性的影响及相关机制研究 [J]. 中国病理生理杂志 , 2019 , 35 ( 4 ): 641 - 645 .
FAYEZ H , EL-MOTALEB M A , SELIM A A . Synergistic cytotoxicity of shikonin‐silver nanoparticles as an opportunity for lung cancer [J]. J Labelled Compd Rad , 2020 , 63 ( 1 ): 25 - 32 .
0
Views
30
下载量
4
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621