基于扶正抗癌理论的温阳散寒中药抗肺癌作用初探
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摘要
目的:基于扶正驱邪抗癌理论探索温阳扶正抗肺癌的临床用药规律,并基于此研究结果初步挖掘温里中药及有效组分在肺癌治疗中的体内外抑瘤作用,为临床的应用提供一定的理论基础。方法:收集挖掘来源1995年-2015年中国知网数据库、维普数据库、万方数据库及Pubmed数据库中收载的温阳散寒类有效内服方剂,进行温阳法治疗恶性肿瘤方剂组方规律分析。并基于此挖掘结果及课题组前期研究结果,体内观察温里中药对Lewis肺癌皮下移植瘤的影响,通过BATMAN分析有效中药的潜在抑瘤单体成分,通过CCK8、细胞划痕实验及流式实验检测有效单体成分的抗肺癌作用情况。结果:共收集文献报道以温阳法治疗恶性肿瘤有效的方剂86首,共包含中药156味,使用频次在10次以上的药物有10味,其中前3位分别为附子、黄芪、甘草,而最常用的临床有效药对为附子与干姜。肺癌皮下移植瘤抑瘤实验结果显示附子与干姜无明显抑瘤作用,而荜茇体内抑瘤作用明显,进一步挖掘结果提示荜茇的有效抗癌单体成分为荜茇明碱,体外A549细胞实验结果提示荜茇明碱有抑制肺癌细胞增殖、促进凋亡和阻断侵袭转移的作用。结论:方剂组方规律的统计分析表明温阳散寒法抗肿瘤并非一家之言,有理论依据并且应用广泛而临床疗效肯定,其组方用药配伍存在一定规律且有生物学抗肺癌依据。
Objective: Based on the theory of ‘strengthening vital qi to eliminate pathogenic factor', to explored the law of clinical drug use of warm yang and strengthening vital qi to eliminate pathogenic factor, and then researched the effects of warm yang medicine and its active ingredients on inhibiting cancer, to provide a theoretical basis for clinical application. Methods: The formula with the function of warming yang for dispelling cold were collected from the China Knowledge Network database, the Vip database, the Wanfang database, and the Pubmed database from 1995 to 2015, to analyze the compatibility regularity of warming yang for dispelling cold in the treatment of malignant tumors. Then, the effects of these drugs on Lewis lung cancer subcutaneous transplanted tumor were observed. The effective anti-tumor monomer components of these were detected by BATMAN analysis. The CCK8, cell scratch test and flow test were used to detect the effect against lung cancer. Results: A total of 86 formula were reported in the literature on the treatment of malignant tumors with the method of warming yang, with 156 traditional Chinese medicines. Among these, 10 herbs were used more than 10 times or more. The first three were used including Radix Aconiti Lateralis Preparata, Radix Astragali seu Hedysari, Radix Glycyrrhizae, and the most commonly used were Radix Aconiti Lateralis Preparata and Rhizoma Zingiberis. The results of anti-tumor experiments on subcutaneously transplanted lung cancer showed that Radix Aconiti Lateralis Preparata and Rhizoma Zingiberis had no effects on the anti-tumor but the Fructus Piperis Longi played a key role in against the tumor. Further research revealed that the scopolamine was the effective anticancer component of Fructus Piperis Longi. Meanwhile, we found that scopolamine inhibits the proliferation of lung cancer cells, promotes apoptosis, and blocks the invasion and metastasis in vitro. Conclusion: The statistic analysis of prescription regularity showes that worming yang for dispelling cold anti-cancer theory is not a single word, it has theoretical basis and certain effect, which is widely used in the clinic. There are certain rules in the compatibility of its prescriptions and the biological anti-lung cancer basis.
Objective: Based on the theory of ‘strengthening vital qi to eliminate pathogenic factor', to explored the law of clinical drug use of warm yang and strengthening vital qi to eliminate pathogenic factor, and then researched the effects of warm yang medicine and its active ingredients on inhibiting cancer, to provide a theoretical basis for clinical application. Methods: The formula with the function of warming yang for dispelling cold were collected from the China Knowledge Network database, the Vip database, the Wanfang database, and the Pubmed database from 1995 to 2015, to analyze the compatibility regularity of warming yang for dispelling cold in the treatment of malignant tumors. Then, the effects of these drugs on Lewis lung cancer subcutaneous transplanted tumor were observed. The effective anti-tumor monomer components of these were detected by BATMAN analysis. The CCK8, cell scratch test and flow test were used to detect the effect against lung cancer. Results: A total of 86 formula were reported in the literature on the treatment of malignant tumors with the method of warming yang, with 156 traditional Chinese medicines. Among these, 10 herbs were used more than 10 times or more. The first three were used including Radix Aconiti Lateralis Preparata, Radix Astragali seu Hedysari, Radix Glycyrrhizae, and the most commonly used were Radix Aconiti Lateralis Preparata and Rhizoma Zingiberis. The results of anti-tumor experiments on subcutaneously transplanted lung cancer showed that Radix Aconiti Lateralis Preparata and Rhizoma Zingiberis had no effects on the anti-tumor but the Fructus Piperis Longi played a key role in against the tumor. Further research revealed that the scopolamine was the effective anticancer component of Fructus Piperis Longi. Meanwhile, we found that scopolamine inhibits the proliferation of lung cancer cells, promotes apoptosis, and blocks the invasion and metastasis in vitro. Conclusion: The statistic analysis of prescription regularity showes that worming yang for dispelling cold anti-cancer theory is not a single word, it has theoretical basis and certain effect, which is widely used in the clinic. There are certain rules in the compatibility of its prescriptions and the biological anti-lung cancer basis.
引文
[1]李和根.刘嘉湘教授以扶正法为主治疗肺癌经验.四川中医,2005(7):5-6
[2]方志红,李雁,徐静,等.扶正祛邪方联合化疗治疗45例晚期非小细胞肺癌临床观察.辽宁中医杂志,2013,40(12):2498-2500
[3]方志红,李雁,李天苗.扶正祛邪方联合化疗治疗晚期非小细胞肺癌疗效分析.时珍国医国药,2013,24(10):2433-2434
[4]方志红,李雁,王艳春,等.扶正祛邪方对肺癌A549细胞EMT的抑制作用及机制研究.中华中医药学刊,2015,33(3):536-538,769
[5]杨佳,李雁.李雁教授从“阴阳平衡”辨治肺癌经验.时珍国医国药,2014,25(2):465-466
[6]李洪霖,李雁.荜茇明碱调控TGF-β1/ERK信号通路抗肺癌作用机制研究.中华中医药杂志,2017,32(5):2149-2153
[7]张波,沈敏鹤,阮善明,等.扶正为主,益气温阳为先--沈敏鹤治肿瘤的经验探究.浙江中医药大学学报,2012,36(10):1086-1088
[8]李雁.刘嘉湘在肺癌治疗中温肾法的运用.中医杂志,2003,44(11):818-820
[9]叶峥嵘,吴琳,环诚,等.基于温阳法治疗肿瘤研究火神派与温补派学术观点区别与联系的理论探讨.辽宁中医杂志,2012,39(7):1282-1283
[10]宋凤丽,朱旭,高辰,等.温阳消水方治疗癌性腹水的临床观察及机制研究.中华中医药杂志,2016,31(4):1513-1516
[11]于莉英,王旭东.“积”病治当温散.中华中医药杂志,2011,26(3):609-610
[12]刘洋,王刚.寒乃生积与不温不散-中医药治疗肿瘤思路的新选择.中医杂志,2009,50(10):954-955
[13]赵远红.恶性肿瘤“温药和之”解析.新中医,2008,40(7):100
[14]周文波,刘丹,高艳菊,等.阳气在恶性肿瘤治疗中的作用简析.中医药学刊,2003,20(7):1182-1183
[15]韦云.恶性肿瘤患者死亡时间与中医阴阳关系的研究.北京中医药大学学报(中医临床版),2008,15(3):5-8
[16]吴雄志,陈丹.温阳散寒药治疗恶性肿瘤机理研究进展.中医研究,2004,17(6):53-54
[17]周洁.温阳经方辨治癌性发热体会.天津中医药,2011,28(6):478-479
[18]Son D J,Kim S Y,Han S S,et al.Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling.Biochem Biophys Res Commun,2012,427(2):349-354
[19]Liu H,Luo R,Chen X,et al.Tissue distribution profiles of three antiparkinsonian alkaloids from Piper longum L.in rats determined byliquid chromatography-tandem mass spectrometry.J Chro-matogr B Analyt Technol Biomed Life Sci,2013,928:78-82
[20]Ku S K,Kim J A,Bae J S.Vascular barrier protective effects of piperlonguminine in vitro and in vivo.Inflamm Res,2014,63(5):369-379
[21]Lee W,Yoo H,Kim J A,et al.Barrier protective effects of piperlonguminine in LPS-induced inflammation in vitro and in vivo.Food Chem Toxicol,2013,58:149-157
[2]方志红,李雁,徐静,等.扶正祛邪方联合化疗治疗45例晚期非小细胞肺癌临床观察.辽宁中医杂志,2013,40(12):2498-2500
[3]方志红,李雁,李天苗.扶正祛邪方联合化疗治疗晚期非小细胞肺癌疗效分析.时珍国医国药,2013,24(10):2433-2434
[4]方志红,李雁,王艳春,等.扶正祛邪方对肺癌A549细胞EMT的抑制作用及机制研究.中华中医药学刊,2015,33(3):536-538,769
[5]杨佳,李雁.李雁教授从“阴阳平衡”辨治肺癌经验.时珍国医国药,2014,25(2):465-466
[6]李洪霖,李雁.荜茇明碱调控TGF-β1/ERK信号通路抗肺癌作用机制研究.中华中医药杂志,2017,32(5):2149-2153
[7]张波,沈敏鹤,阮善明,等.扶正为主,益气温阳为先--沈敏鹤治肿瘤的经验探究.浙江中医药大学学报,2012,36(10):1086-1088
[8]李雁.刘嘉湘在肺癌治疗中温肾法的运用.中医杂志,2003,44(11):818-820
[9]叶峥嵘,吴琳,环诚,等.基于温阳法治疗肿瘤研究火神派与温补派学术观点区别与联系的理论探讨.辽宁中医杂志,2012,39(7):1282-1283
[10]宋凤丽,朱旭,高辰,等.温阳消水方治疗癌性腹水的临床观察及机制研究.中华中医药杂志,2016,31(4):1513-1516
[11]于莉英,王旭东.“积”病治当温散.中华中医药杂志,2011,26(3):609-610
[12]刘洋,王刚.寒乃生积与不温不散-中医药治疗肿瘤思路的新选择.中医杂志,2009,50(10):954-955
[13]赵远红.恶性肿瘤“温药和之”解析.新中医,2008,40(7):100
[14]周文波,刘丹,高艳菊,等.阳气在恶性肿瘤治疗中的作用简析.中医药学刊,2003,20(7):1182-1183
[15]韦云.恶性肿瘤患者死亡时间与中医阴阳关系的研究.北京中医药大学学报(中医临床版),2008,15(3):5-8
[16]吴雄志,陈丹.温阳散寒药治疗恶性肿瘤机理研究进展.中医研究,2004,17(6):53-54
[17]周洁.温阳经方辨治癌性发热体会.天津中医药,2011,28(6):478-479
[18]Son D J,Kim S Y,Han S S,et al.Piperlongumine inhibits atherosclerotic plaque formation and vascular smooth muscle cell proliferation by suppressing PDGF receptor signaling.Biochem Biophys Res Commun,2012,427(2):349-354
[19]Liu H,Luo R,Chen X,et al.Tissue distribution profiles of three antiparkinsonian alkaloids from Piper longum L.in rats determined byliquid chromatography-tandem mass spectrometry.J Chro-matogr B Analyt Technol Biomed Life Sci,2013,928:78-82
[20]Ku S K,Kim J A,Bae J S.Vascular barrier protective effects of piperlonguminine in vitro and in vivo.Inflamm Res,2014,63(5):369-379
[21]Lee W,Yoo H,Kim J A,et al.Barrier protective effects of piperlonguminine in LPS-induced inflammation in vitro and in vivo.Food Chem Toxicol,2013,58:149-157