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百里醌在胰腺癌治疗中的作用
DOI: 10.3969/j.issn.1001-5256.2023.05.036
利益冲突声明：本文不存在任何利益冲突。
作者贡献声明：赵占学负责课题设计，资料分析，撰写论文；李帅、侯晓凡参与收集数据，修改论文；刘林勋、杨金煜负责拟定写作思路，指导撰写文章并最后定稿。
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摘要: 胰腺癌是预后最差的癌症之一，其高转移率和化疗药物耐药性一直是困扰医学界的难题。目前关于百里醌对胰腺癌影响的研究受到了人们的广泛关注，其可以通过抑制癌细胞增殖、促进癌细胞凋亡、抑制侵袭与转移、增强化疗药物敏感性、抗炎等方面发挥对胰腺癌的抗癌作用。该综述简要介绍了国内外对两者关系的研究现状，为下一步的研究提供参考。Abstract: Pancreatic cancer is one of the cancers with the worst prognosis, and its high metastasis rate and resistance to chemotherapy drugs have always been the tough problems in the medical field. At present, the effect of thymoquinone on pancreatic cancer has attracted wide attention, and it can exert an antitumor effect in pancreatic cancer by inhibiting cancer cell proliferation, promoting cancer cell apoptosis, inhibiting invasion and metastasis, enhancing the sensitivity to chemotherapy drugs, and exerting an anti-inflammatory effect. This review briefly introduces the current research status of the association between thymoquinone and pancreatic cancer in China and globally, so as to provide a reference for subsequent research.
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Key words:
- Pancreatic Neoplasms /
- Thymoquinone /
- Therapeutics
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图 1 TQ在胰腺癌中抑制细胞增殖和促进细胞凋亡的作用机制示意图
Figure 1. Schematic diagram of the role of thymoquinone in inhibiting cell proliferation and promoting apoptosis in pancreatic cancer
图 2 TQ抑制胰腺癌侵袭转移机制示意图
Figure 2. Schematic diagram of the role of thymoquinone in inhibiting the invasion and metastasis of pancreatic cancer
图 3 TQ增强胰腺癌化疗敏感性的作用机制示意图
Figure 3. Schematic diagram of the role of thymoquinone in enhancing the chemosensitivity of pancreatic cancer
图 4 TQ在胰腺癌中抗炎作用示意图
Figure 4. Schematic diagram of the anti-inflammatory effects of thymoquinone on pancreatic cancer
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[1] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2018, 68(6): 394-424. DOI: 10.3322/caac.21492. [2] SIEGEL RL, MILLER KD, JEMAL A. Cancer statistics, 2020[J]. CA Cancer J Clin, 2020, 70(1): 7-30. DOI: 10.3322/caac.21590. [3] SUN D, CAO M, LI H, et al. Cancer burden and trends in China: A review and comparison with Japan and South Korea[J]. Chin J Cancer Res, 2020, 32(2): 129-139. DOI: 10.21147/j.issn.1000-9604.2020.02.01. [4] Pancreatic Disease Collaborative Group, Chinese Society of Digestive Endoscopy. Chinese consensus on the early screening and surveillance for pancreatic cancer in high-risk individuals (2021, Nanjing)[J]. J Clin Hepatol, 2022, 38(5): 1016-1022. DOI: 10.3969/j.issn.1001-5256.2022.05.008.中华医学会消化内镜学分会胰腺疾病协作组. 中国胰腺癌高危人群早期筛查和监测共识意见(2021, 南京)[J]. 临床肝胆病杂志, 2022, 38(5): 1016-1022. DOI: 10.3969/j.issn.1001-5256.2022.05.008. [5] SHAFODINO FS, LUSILAO JM, MWAPAGHA LM. Phytochemical characterization and antimicrobial activity of Nigella sativa seeds[J]. PLoS One, 2022, 17(8): e0272457. DOI: 10.1371/journal.pone.0272457. [6] LIU Y, HUANG L, KIM MY, et al. The role of thymoquinone in inflammatory response in chronic diseases[J]. Int J Mol Sci, 2022, 23(18): 10246. DOI: 10.3390/ijms231810246. [7] ALAM M, HASAN GM, ANSAIR MM, et al. Therapeutic implications and clinical manifestations of thymoquinone. Phytochemistry[J]. 2022, 200: 113213. DOI: 10.1016/j.phytochem.2022.113213 .[8] JAIN A, POOLADANDA V, BULBAKE U, et al. Liposphere mediated topical delivery of thymoquinone in the treatment of psoriasis[J]. Nanomedicine, 2017, 13(7): 2251-2262. DOI: 10.1016/j.nano.2017.06.009. [9] PANG J, SHEN N, YAN F, et al. Thymoquinone exerts potent growth-suppressive activity on leukemia through DNA hypermethylation reversal in leukemia cells[J]. Oncotarget, 2017, 8(21): 34453-34467. DOI: 10.18632/oncotarget.16431. [10] ALMAJALI B, AL-JAMAL H, TAIB W, et al. Thymoquinone, as a novel therapeutic candidate of cancers[J]. Pharmaceuticals (Basel), 2021, 14(4): 369. DOI: 10.3390/ph14040369. [11] KANTER M. Thymoquinone attenuates lung injury induced by chronic toluene exposure in rats[J]. Toxicol Ind Health, 2011, 27(5): 387-395. DOI: 10.1177/0748233710387630. [12] TAN M, NORWOOD A, MAY M, et al. Effects of (-)epigallocatechin gallate and thymoquinone on proliferation of a PANC-1 cell line in culture[J]. Biomed Sci Instrum, 2006, 42: 363-371. [13] TORRES MP, PONNUSAMY MP, CHAKRABORTY S, et al. Effects of thymoquinone in the expression of mucin 4 in pancreatic cancer cells: implications for the development of novel cancer therapies[J]. Mol Cancer Ther, 2010, 9(5): 1419-1431. DOI: 10.1158/1535-7163.MCT-10-0075. [14] NARAYANAN P, FARGHADANI R, NYAMATHULLA S, et al. Natural quinones induce ROS-mediated apoptosis and inhibit cell migration in PANC-1 human pancreatic cancer cell line[J]. J Biochem Mol Toxicol, 2022, 36(5): e23008. DOI: 10.1002/jbt.23008. [15] RELLES D, CHIPITSYNA GI, GONG Q, et al. Thymoquinone promotes pancreatic cancer cell death and reduction of tumor size through combined inhibition of histone deacetylation and induction of histone acetylation[J]. Adv Prev Med, 2016, 2016: 1407840. DOI: 10.1155/2016/1407840. [16] IMRAN M, RAUF A, KHAN IA, et al. Thymoquinone: A novel strategy to combat cancer: A review[J]. Biomed Pharmacother, 2018(106): 390-402. DOI: 10.1016/j.biopha.2018.06.159. [17] MU GG, ZHANG LL, LI HY, et al. Thymoquinone pretreatment overcomes the insensitivity and potentiates the antitumor effect of gemcitabine through abrogation of Notch1, PI3K/Akt/mTOR regulated signaling pathways in pancreatic cancer[J]. Dig Dis Sci, 2015, 60(4): 1067-1080. DOI: 10.1007/s10620-014-3394-x. [18] KARKI N, AGGARWAL S, LAINE RA, et al. Cytotoxicity of juglone and thymoquinone against pancreatic cancer cells[J]. Chem Biol Interact, 2020, 327: 109142. DOI: 10.1016/j.cbi.2020.109142. [19] MAHMOUD YK, ABDELRAZEK H. Cancer: Thymoquinone antioxidant/pro-oxidant effect as potential anticancer remedy[J]. Biomed Pharmacother, 2019, 115: 108783. DOI: 10.1016/j.biopha.2019.108783. [20] WU ZH, CHEN Z, SHEN Y, et al. Anti-metastasis effect of thymoquinone on human pancreatic cancer[J]. Acta Pharm Sin, 2011, 46(8): 910-914.吴志豪, 陈兆, 沈跃, 等. 百里醌抑制体内外胰腺癌转移作用[J]. 药学学报, 2011, 46(8): 910-914. [21] WANG YM. Inhibitory effects of thymoquinone on human pancreatic carcinoma orthotopically implanted in nude mice[J]. Nat Med J China, 2011, 91(44): 3111-3114. DOI: 10.3760/cma.j.issn.0376-2491.2011.44.005.王咏梅. 百里醌抑制胰腺癌裸鼠原位移植瘤生长的实验观察[J]. 中华医学杂志, 2011, 91(44): 3111-3114. DOI: 10.3760/cma.j.issn.0376-2491.2011.44.005. [22] MU GG, YU HG, LI HY, et al. Thymoquinone inhibits migration and invasion of human pancreatic cancer BxPC-3 cells in vitro[J]. Chin J Gastroenterol, 2014, 19(11): 650-654. DOI: 10.3969/j.issn.1008-7125.2014.11.003.慕刚刚, 于红刚, 李红艳, 等. 百里醌抑制人胰腺癌BxPC-3细胞体外运动和侵袭的研究[J]. 胃肠病学, 2014, 19(11): 650-654. DOI: 10.3969/j.issn.1008-7125.2014.11.003. [23] FURUKAWA T. Mechanisms of development and progression of pancreatic neoplasms[J]. Pathol Int, 2022, 72(11): 529-540. DOI: 10.1111/pin.13272. [24] SPALLAROSSA A, TASSO B, RUSSO E, et al. The development of FAK inhibitors: A five-year update[J]. Int J Mol Sci, 2022, 23(12): 6381. DOI: 10.3390/ijms23126381. [25] MU GG, YU HG, LI HY, et al. Thymoquinone potentiates antitumor activity of gemcitabine in pancreatic cancer BxPC-3 cells in vitro[J]. J Med Res, 2014, 43(9): 72-76.慕刚刚, 于红刚, 李红艳, 等. 百里醌联合吉西他滨对胰腺癌BxPC-3细胞体外生长的影响[J]. 医学研究杂志, 2014, 43(9): 72-76. [26] BANERJEE S, KASEB AO, WANG Z, et al. Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer[J]. Cancer Res, 2009, 69(13): 5575-5583. DOI: 10.1158/0008-5472.CAN-08-4235. [27] PANDITA A, KUMAR B, MANVATI S, et al. Synergistic combination of gemcitabine and dietary molecule induces apoptosis in pancreatic cancer cells and down regulates PKM2 expression[J]. PLoS One, 2014, 9(9): e107154. DOI: 10.1371/journal.pone.0107154. [28] PANDITA A, MANVATI S, SINGH SK, et al. Combined effect of microRNA, nutraceuticals and drug on pancreatic cancer cell lines[J]. Chem Biol Interact, 2015, 233: 56-64. DOI: 10.1016/j.cbi.2015.03.018. [29] WU ZH, XU Y, WANG ZH, et al. Effects of thymoquinone combined with gemcitabine on growth and apoptosis of human pancreatic cancer cell line BxPC-3[J]. Modern Pract Med, 2014, 10(6): 1242-1243. DOI: 10.3969/j.issn.1671-0800.2014.10.028吴志豪, 许远, 王兆洪, 等. 百里醌联合吉西他滨对人胰腺癌细胞株BxPC-3生长和凋亡的影响[J]. 现代实用医学, 2014, 10(6): 1242-1243. DOI: 10.3969/j.issn.1671-0800.2014.10.028. [30] CUI J, GUO Y, WU H, et al. Everolimus regulates the activity of gemcitabine-resistant pancreatic cancer cells by targeting the Warburg effect via PI3K/AKT/mTOR signaling[J]. Mol Med, 2021, 27(1): 38. DOI: 10.1186/s10020-021-00300-8. [31] ANSARY J, GIAMPIERI F, FORBES-HERNANDEZ TY, et al. Nutritional value and preventive role of nigella sativa L. and its main component thymoquinone in cancer: An evidenced-based review of preclinical and clinical studies[J]. Molecules, 2021, 26(8): 2108. DOI: 10.3390/molecules26082108. [32] TALBERT EE, LEWIS HL, FARREN MR, et al. Circulating monocyte chemoattractant protein-1 (MCP-1) is associated with cachexia in treatment-naïve pancreatic cancer patients[J]. J Cachexia Sarcopenia Muscle, 2018, 9(2): 358-368. DOI: 10.1002/jcsm.12251. [33] LIU A, WANG W, CHEN Z, et al. Anti-angiogenic effect of thymoquinone on angiogenesis and proliferation of pancreatic cancer[J]. Chin J Pathophysiol, 2011, 27(12): 2281-2285. DOI: 10.3969/j.issn.1000-4718.2011.12.008.刘岸, 王武, 陈兆, 等. 百里醌对血管生成及胰腺癌生长的影响[J]. 中华病理生理杂志, 2011, 27(12): 2281-2285. DOI: 10.3969/j.issn.1000-4718.2011.12.008. [34] BANERJEE S, AZMI AS, PADHYE S, et al. Structure-activity studies on therapeutic potential of Thymoquinone analogs in pancreatic cancer[J]. Pharm Res, 2010, 27(6): 1146-1158. DOI: 10.1007/s11095-010-0145-3. [35] RACHAMALLA HK, BHATTACHARYA S, AHMAD A, et al. Enriched pharmacokinetic behavior and antitumor efficacy of thymoquinone by liposomal delivery[J]. Nanomedicine (Lond), 2021, 16(8): 641-656. DOI: 10.2217/nnm-2020-0470. [36] BALLOUT F, HABLI Z, RAHAL ON, et al. Thymoquinone-based nanotechnology for cancer therapy: promises and challenges[J]. Drug Discov Today, 2018, 23(5): 1089-1098. DOI: 10.1016/j.drudis.2018.01.043. [37] RAMACHANDRAN S, THANGARAJAN S. Thymoquinone loaded solid lipid nanoparticles counteracts 3-Nitropropionic acid induced motor impairments and neuroinflammation in rat model of Huntington's disease[J]. Metab Brain Dis, 2018, 33(5): 1459-1470. DOI: 10.1007/s11011-018-0252-0. [38] SINGH A, AHMAD I, AKHTER S, et al. Nanocarrier based formulation of Thymoquinone improves oral delivery: stability assessment, in vitro and in vivo studies[J]. Colloids Surf B Biointerfaces, 2013, 102: 822-832. DOI: 10.1016/j.colsurfb.2012.08.038. [39] NG WK, SAIFUL YAZAN L, YAP LH, et al. Thymoquinone-loaded nanostructured lipid carrier exhibited cytotoxicity towards breast cancer cell lines (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa)[J]. Biomed Res Int, 2015, 2015: 263131. DOI: 10.1155/2015/263131. [40] ABDELWAHAB SI, SHEIKH BY, TAHA MM, et al. Thymoquinone-loaded nanostructured lipid carriers: preparation, gastroprotection, in vitro toxicity, and pharmacokinetic properties after extravascular administration[J]. Int J Nanomedicine, 2013, 8: 2163-2172. DOI: 10.2147/IJN.S44108. [41] RATHORE C, UPADHYAY N, KAUNDAL R, et al. Enhanced oral bioavailability and hepatoprotective activity of thymoquinone in the form of phospholipidic nano-constructs[J]. Expert Opin Drug Deliv, 2020, 17(2): 237-253. DOI: 10.1080/17425247.2020.1716728. [42] BHATTACHARYA S, AHIR M, PATRA P, et al. PEGylated-thymoquinone-nanoparticle mediated retardation of breast cancer cell migration by deregulation of cytoskeletal actin polymerization through miR-34a[J]. Biomaterials, 2015, 51: 91-107. DOI: 10.1016/j.biomaterials.2015.01.007. [43] VERMA SK, RASTOGI S, JAVED K, et al. Nanothymoquinone, a novel hepatotargeted delivery system for treating CCl4 mediated hepatotoxicity in rats[J]. J Mater Chem B, 2013, 1(23): 2956-2966. DOI: 10.1039/c3tb20379d. [44] ABU-DAHAB R, ODEH F, ISMAIL SI, et al. Preparation, characterization and antiproliferative activity of thymoquinone-beta-cyclodextrin self assembling nanoparticles[J]. Pharmazie, 2013, 68(12): 939-944. [45] ODEH F, ISMAIL SI, ABU-DAHAB R, et al. Thymoquinone in liposomes: a study of loading efficiency and biological activity towards breast cancer[J]. Drug Deliv, 2012, 19(8): 371-377. DOI: 10.3109/10717544.2012.727500. [46] General Office of National Health Commission. Standard for diagnosis and treatment of pancreatic cancer (2022 edition)[J]. J Clin Hepatol, 2022, 38(5): 1006-1015. DOI: 10.3969/j.issn.1001-5256.2022.05.007.国家卫生健康委办公厅. 胰腺癌诊疗指南(2022年版)[J]. 临床肝胆病杂志, 2022, 38(5): 1006-1015. DOI: 10.3969/j.issn.1001-5256.2022.05.007. [47] WANG D, CUI M, YU J. Research advances of precision treatment for pancreatic cancer[J]. Chin J Dig Surg, 2021, 20(4): 385-394. DOI: 10.3760/cma.j.cn115610-20210223-00089.汪栋, 崔铭, 余俊. 胰腺癌精准治疗的研究进展[J]. 中华消化外科杂志, 2021, 20(4): 385-394. DOI: 10.3760/cma.j.cn115610-20210223-00089. [48] ZHANG TP, LIU YZ, REN B. Current status and challenges of total neoadjuvant therapy for pancreatic cancer[J]. Chin J Dig Surg, 2022, 21(4): 461-464. DOI: 10.3760/cma.j.cn115610-20220320-00141.张太平, 刘悦泽, 任博. 胰腺癌全程新辅助治疗的现状及挑战[J]. 中华消化外科杂志, 2022, 21(4): 461-464. DOI: 10.3760/cma.j.cn115610-20220320-00141. [49] BUTNARIU M, QUISPE C, HERRERA-BRAVO J, et al. The effects of thymoquinone on pancreatic cancer: Evidence from preclinical studies[J]. Biomed Pharmacother, 2022, 153: 113364. DOI: 10.1016/j.biopha.2022.113364. -
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