中药促凋亡机制干预甲状腺癌的实验研究进展
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摘要
甲状腺癌是内分泌系统的常见恶性肿瘤,近年来发病率有上升趋势,中药在甲状腺癌的治疗中发挥着独特的作用,越来越多的实验研究表明促细胞凋亡是中药治疗甲状腺癌的重要效应机制。本文从下调抗凋亡基因Bcl-2、调节Bcl-2/Bax平衡、抑制c Myc基因表达、下调Survivin基因和蛋白表达、抑制P13K/AKT信号通路、下调PARP的水平和抑制MAPK信号通路等不同方面,对中药治疗甲状腺癌的促凋亡机制作了总结,以期以后深入的实验及临床研究提供基础。
Thyroid cancer is a common malignant tumor of the endocrine system. In recent years, the incidence rate has an increasing trend. Traditional Chinese medicine plays a unique role in the treatment of thyroid cancer. More and more experimental studies have shown that pro-apoptosis is an important mechanism in the treatment of thyroid cancer with traditional Chinese medicine. This article summarizes the pro-apoptotic mechanism of traditional Chinese medicine in the treatment of thyroid cancer, including down-regulating anti-apoptotic gene BCL-2, regulating Bcl-2/Bax balance,inhibiting cMyc gene expression, downpathway, down-regulates PARP levels, and inhibits MAPK signaling pathway. etc., so as to provide a basis of in-depth experimental and clinical research.
Thyroid cancer is a common malignant tumor of the endocrine system. In recent years, the incidence rate has an increasing trend. Traditional Chinese medicine plays a unique role in the treatment of thyroid cancer. More and more experimental studies have shown that pro-apoptosis is an important mechanism in the treatment of thyroid cancer with traditional Chinese medicine. This article summarizes the pro-apoptotic mechanism of traditional Chinese medicine in the treatment of thyroid cancer, including down-regulating anti-apoptotic gene BCL-2, regulating Bcl-2/Bax balance,inhibiting cMyc gene expression, downpathway, down-regulates PARP levels, and inhibits MAPK signaling pathway. etc., so as to provide a basis of in-depth experimental and clinical research.
引文
1 Nix P, Nicolaides A, Coatesworth A P. Thyroid cancer review 1:presentation and investigation of thyroid cancer. International Journal of Clinical Practice, 2005, 59(11):1340-1344.
2 Chen W, Zheng R, Baade P D, et al. Cancer statistics in China, 2015.CA:a Cancer Journal for Clinicians, 2016, 66(2):115-132.
3 Call J A, Eckhardt S G, Camidge D R. Targeted manipulation of apoptosis incancertreatment.The Lancet Oncology, 2008,9(10):1002-1011.
4 Fulda S, Debatin K M. Targeting Apoptosis Pathways in Cancer Therapy.Current Cancer Drug Targets, 2004, 4(7):569-576.
5 Polkinghorne K R, Seneviratne M, Kerr P G. Effect of a vascular access nurse coordinator to reduce central venous catheter use in incident hemodialysis patients:a quality improvement report. American Journal of Kidney Diseases:the Official Journal of the National Kidney Foundation,2009, 53(1):99-106.
6 高虹,丛琦,全成实,等.甲状腺癌组织中凋亡相关蛋白Fas, FasL,Bcl-2和Bax的表达及意义.实用肿瘤学杂志, 2005, 19(4):273-275.
7 Reed J C. Bcl-2 and the regulation of programmed cell death. The Journal of Cell Biology, 1994, 124(1-2):1-6.
8 Reed J C. Bcl-2 family proteins:regulators of apoptosis and chemoresistance in hematologic malignancies. Seminars in Hematology,1997, 34(4 Suppl 5):9-19.
9 熊燚,赵敏,谭剑斌,等.夏枯草对人甲状腺髓样癌细胞增殖的影响和诱导其凋亡的作用机制.中华中医药杂志,2018,33(8):3379-3384.
10 吴俊林,卢德成,罗佐杰,等.中药山慈姑对甲状腺癌细胞的促凋亡作用.时珍国医国药, 2014, 25(1):71-74.
11 Scorrano L, Korsmeyer S J. Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochemical and Biophysical Research Communications, 2003, 304(3):437-444.
12 Martinez-Brocca M A, Castilla C, Navarro E, et al. Clinical pathological correlations of Bcl-xL and Bax expression in differentiated thyroid carcinoma. Clinical Endocrinology, 2008, 68(2):190-7.
13 熊燚,赵敏,谭剑斌,等.夏枯草诱导人甲状腺乳头状癌细胞K1增殖和凋亡的影响及其作用机制.现代生物医学进展, 2017, 17(13):2401-2406.
14 孙巍.姜黄素对人甲状腺癌B-CPAP细胞生物学行为的影响.现代肿瘤医学, 2019, 27(2):183-187.
15 Brooks T A, Hurley L H. The role of supercoiling in transcriptional control of MYC and its importance in molecular therapeutics. Nature Reviews Cancer, 2009, 9(12):849-861.
16 CandasD,FanM,NantajitD, et al.Cyclin B1/Cdk1phosphorylatesmitochondrial antioxidant MnSOD in cell adaptive response to radiation stress. Journal of Molecular Cell Biology, 2013, 5(3):166-175.
17 Sun L, Song L, Wan Q, et al. c Myc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions.Cell Research, 2015, 25(4):429.
18 伍庆华,李龙雪,宋渺渺,等.中药玄参对甲状腺癌SW579细胞增殖及BCL-2和C-myc表达的影响.江西中医药, 2018, 49(10):67-69.
19 吴俊林,卢德成,罗佐杰,等.山慈姑对甲状腺癌SW579细胞BCL-2和C-myc表达的影响.广东医学, 2014, 35(3):360-363.
20 Giodini A, Kallio M J, Wall N R, et al. Regulation of microtubule stability and mitotic progression by survivin. Cancer Research, 2002, 62(9):2462-2467.
21 Tran J, Master Z, Yu J L, et al. A role for survivin in chemoresistance of endothelial cells mediated by VEGF. Proceedings of the National Academy of Sciences of the United States of America,2002,99(7):4349-4354.
22 Morgillo F, Woo J K, Kim E S, et al. Heterodimerization of insulin-like growth factor receptor/epidermal growth factor receptor and induction of survivin expression counteract the antitumor action of erlotinib. Cancer Research, 2006, 66(20):10100-10011.
23 Pannone G, Santoro A, Pasquali D, et al. The role of survivin in thyroid tumors:differences of expression in well-differentiated, non-welldifferentiated, and anaplastic thyroid cancers. Thyroid:Official Journal of the American Thyroid Association, 2014, 24(3):511-519.
24 许珂玉,肖建英.五味子多糖对甲状腺癌细胞株SW579凋亡及survivin表达的影响.吉林大学学报(医学版),2011,37(2):279-83+394.
25 赵艳,褚晓杰,朴宏鹰,等.黄药子对甲状腺癌细胞株SW579 Survivin基因和蛋白表达的影响.中国中医药科技, 2012, 19(4):320-321.
26 Tirro E, Consoli M L, Massimino M, et al. Altered expression of c-IAP1,survivin, and Smac contributes to chemotherapy resistance in thyroid cancer cells. Cancer Research, 2006, 66(8):4263-4272.
27 Wu Y R, Qi H J, Deng D F, et al. MicroRNA-21 promotes cell proliferation, migration, and resistance to apoptosis through PTEN/PI3K/AKT signaling pathway in esophageal cancer. Tumour Biology:the Journal of the International Society for Oncodevelopmental Biology and Medicine, 2016, 37(9):12061-12070.
28 Karakas B, Bachman K E, Park B H. Mutation of the PIK3CA oncogene in human cancers. British Journal of Cancer, 2006, 94(4):455-459.
29 Hervieu A, Kermorgant S. The role of PI3K in met driven cancer:a recap. Frontiers in Molecular Biosciences, 2018, 5:86.
30 Hou P, Liu D, Shan Y, et al. Genetic Alterations and Their Relationship in the Phosphatidylinositol 3-Kinase/Akt Pathway in Thyroid Cancer.Clinical Cancer Research, 2007, 13(4):1161-1170.
31 Sansal I, Sellers W R. The biology and clinical relevance of the PTEN tumor suppressor pathway. Journal of Clinical Oncology, 2004, 22(14):2954-2963.
32 王卫红,王贵锋,王丽,等.葛根素调控PI3K/AKT信号对甲状腺癌细胞凋亡及机制研究.中药材, 2018(10):2188-2191.
33 Li L, Wang X, Sharvan R, et al. Berberine could inhibit thyroid carcinoma cells by inducing mitochondrial apoptosis, G0/G1 cell cycle arrest and suppressing migration via PI3K-AKT and MAPK signaling pathways.Biomedecine&Pharmacotherapie, 2017, 95:1225-1231.
34 Peralta-Leal A, Rodriguez-Vargas JM, Aguilar-Quesada R, et al. PARP inhibitors:new partners in the therapy of cancer and inflammatory diseases. Free radical biology&medicine, 2009, 47(1):13-26.
35 LaFargue CJ, Dal Molin GZ, Sood AK, et al. Exploring and comparing adverse events between PARP inhibitors. The Lancet Oncology, 2019, 20(1):e15-e28.
36 Albert J M, Cao C, Kim K W, et al. Inhibition of poly(ADP-ribose)polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models. Clin Cancer Res, 2007, 13(10):3033-3042.
37 Kummar S, Chen A, Ji J, et al. Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas. Cancer research, 2011, 71(17):5626-5634.
38 Ju BG, Lunyak VV, Perissi V, et al. A topoisomerase IIbeta-mediated dsDNA break required for regulated transcription. Science, 2006, 312(5781):1798-1802.
39 Knudsen KE, Scher HI. Starving the addiction:new opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res,2009, 15(15):4792-8.
40 Lavarone E, Puppin C, Passon N, et al. The PARP inhibitor PJ34 modifies proliferation, NIS expression and epigenetic marks in thyroid cancer cell lines. Molecular and cellular endocrinology, 2013,365(1):1-10.
41 杨丹丽,张迎秋,李媛,等.冬凌草甲素对甲状腺癌BCPAP细胞增殖的抑制作用.大连医科大学学报, 2016, 38(4):330-333.
42 Chen Y, Chen YC, Lin YT, et al. Cordycepin induces apoptosis of CGTH W-2 thyroid carcinoma cells through the calcium-calpain-caspase 7-PARP pathway. Journal of agricultural and food chemistry, 2010, 58(22):11645-52.
43 HF P, R S, MA K, et al. mTOR and MAPK:from localized translation control to epilepsy. BMC neuroscience, 2016, 17(1):73.
44 AC H, ML T, D R. Oncogenic AKTivation of translation as a therapeutic target. British journal of cancer, 2011, 105(3):329-336.
45 C N, J L, S P. BRAF(V600E)and microenvironment in thyroid cancer:a functional link to drive cancer progression. Cancer research, 2011, 71(7):2417-2422.
46 Song F, Zhang L, Yu HX, et al. The mechanism underlying proliferationinhibitory and apoptosis-inducing effects of curcumin on papillary thyroid cancer cells. Food chemistry, 2012, 132(1):43-50.
2 Chen W, Zheng R, Baade P D, et al. Cancer statistics in China, 2015.CA:a Cancer Journal for Clinicians, 2016, 66(2):115-132.
3 Call J A, Eckhardt S G, Camidge D R. Targeted manipulation of apoptosis incancertreatment.The Lancet Oncology, 2008,9(10):1002-1011.
4 Fulda S, Debatin K M. Targeting Apoptosis Pathways in Cancer Therapy.Current Cancer Drug Targets, 2004, 4(7):569-576.
5 Polkinghorne K R, Seneviratne M, Kerr P G. Effect of a vascular access nurse coordinator to reduce central venous catheter use in incident hemodialysis patients:a quality improvement report. American Journal of Kidney Diseases:the Official Journal of the National Kidney Foundation,2009, 53(1):99-106.
6 高虹,丛琦,全成实,等.甲状腺癌组织中凋亡相关蛋白Fas, FasL,Bcl-2和Bax的表达及意义.实用肿瘤学杂志, 2005, 19(4):273-275.
7 Reed J C. Bcl-2 and the regulation of programmed cell death. The Journal of Cell Biology, 1994, 124(1-2):1-6.
8 Reed J C. Bcl-2 family proteins:regulators of apoptosis and chemoresistance in hematologic malignancies. Seminars in Hematology,1997, 34(4 Suppl 5):9-19.
9 熊燚,赵敏,谭剑斌,等.夏枯草对人甲状腺髓样癌细胞增殖的影响和诱导其凋亡的作用机制.中华中医药杂志,2018,33(8):3379-3384.
10 吴俊林,卢德成,罗佐杰,等.中药山慈姑对甲状腺癌细胞的促凋亡作用.时珍国医国药, 2014, 25(1):71-74.
11 Scorrano L, Korsmeyer S J. Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochemical and Biophysical Research Communications, 2003, 304(3):437-444.
12 Martinez-Brocca M A, Castilla C, Navarro E, et al. Clinical pathological correlations of Bcl-xL and Bax expression in differentiated thyroid carcinoma. Clinical Endocrinology, 2008, 68(2):190-7.
13 熊燚,赵敏,谭剑斌,等.夏枯草诱导人甲状腺乳头状癌细胞K1增殖和凋亡的影响及其作用机制.现代生物医学进展, 2017, 17(13):2401-2406.
14 孙巍.姜黄素对人甲状腺癌B-CPAP细胞生物学行为的影响.现代肿瘤医学, 2019, 27(2):183-187.
15 Brooks T A, Hurley L H. The role of supercoiling in transcriptional control of MYC and its importance in molecular therapeutics. Nature Reviews Cancer, 2009, 9(12):849-861.
16 CandasD,FanM,NantajitD, et al.Cyclin B1/Cdk1phosphorylatesmitochondrial antioxidant MnSOD in cell adaptive response to radiation stress. Journal of Molecular Cell Biology, 2013, 5(3):166-175.
17 Sun L, Song L, Wan Q, et al. c Myc-mediated activation of serine biosynthesis pathway is critical for cancer progression under nutrient deprivation conditions.Cell Research, 2015, 25(4):429.
18 伍庆华,李龙雪,宋渺渺,等.中药玄参对甲状腺癌SW579细胞增殖及BCL-2和C-myc表达的影响.江西中医药, 2018, 49(10):67-69.
19 吴俊林,卢德成,罗佐杰,等.山慈姑对甲状腺癌SW579细胞BCL-2和C-myc表达的影响.广东医学, 2014, 35(3):360-363.
20 Giodini A, Kallio M J, Wall N R, et al. Regulation of microtubule stability and mitotic progression by survivin. Cancer Research, 2002, 62(9):2462-2467.
21 Tran J, Master Z, Yu J L, et al. A role for survivin in chemoresistance of endothelial cells mediated by VEGF. Proceedings of the National Academy of Sciences of the United States of America,2002,99(7):4349-4354.
22 Morgillo F, Woo J K, Kim E S, et al. Heterodimerization of insulin-like growth factor receptor/epidermal growth factor receptor and induction of survivin expression counteract the antitumor action of erlotinib. Cancer Research, 2006, 66(20):10100-10011.
23 Pannone G, Santoro A, Pasquali D, et al. The role of survivin in thyroid tumors:differences of expression in well-differentiated, non-welldifferentiated, and anaplastic thyroid cancers. Thyroid:Official Journal of the American Thyroid Association, 2014, 24(3):511-519.
24 许珂玉,肖建英.五味子多糖对甲状腺癌细胞株SW579凋亡及survivin表达的影响.吉林大学学报(医学版),2011,37(2):279-83+394.
25 赵艳,褚晓杰,朴宏鹰,等.黄药子对甲状腺癌细胞株SW579 Survivin基因和蛋白表达的影响.中国中医药科技, 2012, 19(4):320-321.
26 Tirro E, Consoli M L, Massimino M, et al. Altered expression of c-IAP1,survivin, and Smac contributes to chemotherapy resistance in thyroid cancer cells. Cancer Research, 2006, 66(8):4263-4272.
27 Wu Y R, Qi H J, Deng D F, et al. MicroRNA-21 promotes cell proliferation, migration, and resistance to apoptosis through PTEN/PI3K/AKT signaling pathway in esophageal cancer. Tumour Biology:the Journal of the International Society for Oncodevelopmental Biology and Medicine, 2016, 37(9):12061-12070.
28 Karakas B, Bachman K E, Park B H. Mutation of the PIK3CA oncogene in human cancers. British Journal of Cancer, 2006, 94(4):455-459.
29 Hervieu A, Kermorgant S. The role of PI3K in met driven cancer:a recap. Frontiers in Molecular Biosciences, 2018, 5:86.
30 Hou P, Liu D, Shan Y, et al. Genetic Alterations and Their Relationship in the Phosphatidylinositol 3-Kinase/Akt Pathway in Thyroid Cancer.Clinical Cancer Research, 2007, 13(4):1161-1170.
31 Sansal I, Sellers W R. The biology and clinical relevance of the PTEN tumor suppressor pathway. Journal of Clinical Oncology, 2004, 22(14):2954-2963.
32 王卫红,王贵锋,王丽,等.葛根素调控PI3K/AKT信号对甲状腺癌细胞凋亡及机制研究.中药材, 2018(10):2188-2191.
33 Li L, Wang X, Sharvan R, et al. Berberine could inhibit thyroid carcinoma cells by inducing mitochondrial apoptosis, G0/G1 cell cycle arrest and suppressing migration via PI3K-AKT and MAPK signaling pathways.Biomedecine&Pharmacotherapie, 2017, 95:1225-1231.
34 Peralta-Leal A, Rodriguez-Vargas JM, Aguilar-Quesada R, et al. PARP inhibitors:new partners in the therapy of cancer and inflammatory diseases. Free radical biology&medicine, 2009, 47(1):13-26.
35 LaFargue CJ, Dal Molin GZ, Sood AK, et al. Exploring and comparing adverse events between PARP inhibitors. The Lancet Oncology, 2019, 20(1):e15-e28.
36 Albert J M, Cao C, Kim K W, et al. Inhibition of poly(ADP-ribose)polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models. Clin Cancer Res, 2007, 13(10):3033-3042.
37 Kummar S, Chen A, Ji J, et al. Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas. Cancer research, 2011, 71(17):5626-5634.
38 Ju BG, Lunyak VV, Perissi V, et al. A topoisomerase IIbeta-mediated dsDNA break required for regulated transcription. Science, 2006, 312(5781):1798-1802.
39 Knudsen KE, Scher HI. Starving the addiction:new opportunities for durable suppression of AR signaling in prostate cancer. Clin Cancer Res,2009, 15(15):4792-8.
40 Lavarone E, Puppin C, Passon N, et al. The PARP inhibitor PJ34 modifies proliferation, NIS expression and epigenetic marks in thyroid cancer cell lines. Molecular and cellular endocrinology, 2013,365(1):1-10.
41 杨丹丽,张迎秋,李媛,等.冬凌草甲素对甲状腺癌BCPAP细胞增殖的抑制作用.大连医科大学学报, 2016, 38(4):330-333.
42 Chen Y, Chen YC, Lin YT, et al. Cordycepin induces apoptosis of CGTH W-2 thyroid carcinoma cells through the calcium-calpain-caspase 7-PARP pathway. Journal of agricultural and food chemistry, 2010, 58(22):11645-52.
43 HF P, R S, MA K, et al. mTOR and MAPK:from localized translation control to epilepsy. BMC neuroscience, 2016, 17(1):73.
44 AC H, ML T, D R. Oncogenic AKTivation of translation as a therapeutic target. British journal of cancer, 2011, 105(3):329-336.
45 C N, J L, S P. BRAF(V600E)and microenvironment in thyroid cancer:a functional link to drive cancer progression. Cancer research, 2011, 71(7):2417-2422.
46 Song F, Zhang L, Yu HX, et al. The mechanism underlying proliferationinhibitory and apoptosis-inducing effects of curcumin on papillary thyroid cancer cells. Food chemistry, 2012, 132(1):43-50.