龙葵总碱对骨髓瘤细胞凋亡及凋亡相关因子NF-κB表达的影响
|
摘要
龙葵总碱对骨髓瘤细胞凋亡及调亡相关因子NF-κ B表达的影响
目的：本研究以人骨髓瘤细胞株RPMI8226为研究对象,从两个方面观察龙葵总碱的作用：第一,观察龙葵总碱对骨髓瘤细胞株RPMI8226的促凋亡作用。第二,观察龙葵总碱对多发性骨髓瘤NF-κB表达的影响,旨在从分子水平初步揭示其抗MM的作用机制,为其进行体内抗MM实验提供重要的实验依据,为研制开发具有抗MM作用的中药新药制剂奠定科学基础。
方法：选用人骨髓瘤RPMI-8226细胞株为研究对象,以龙葵总碱为被试对象,采用MTT法检测细胞增殖活性,AnnexinV-FITC/P I双标记法分析细胞凋亡的改变；免疫荧光细胞化学染色分析NF-κ B的表达情况,探讨龙葵总碱对人骨髓瘤RPMI-8226细胞的凋亡作用以及对NF-κ B表达的影响。
结果：1.在25mg/L龙葵总碱处理RPMI-8226细胞48h后,RPMI8226细胞的生长出现明显的抑制作用,且随着浓度加大及时间延长,其抑制作用逐步增强。
2.药物浓度<25mg/L时,诱导凋亡作用不明显,当药物浓度达到25mg/L早期凋亡明显增多
3.当药物浓度达25mg/L(此时细胞凋亡明显)时,NFκ B表达水平的降低具有统计学意义。
结论：1.龙葵总碱可抑制人多发性骨髓瘤RPMI-8226细胞增殖,促进细胞凋亡,并且呈剂量和时间依赖性。2.NF-κ B表达量在人多发性骨髓瘤RPMI-8226细胞株随龙葵总碱的药物浓度增大而降低。
Solanum nigrum alkaloids myeloma cell apoptosis and apoptosis related genes of NF-kB
Objective:This study of human multiple myeloma cell strains RPMI8226, to observe the role of Solanum nigrum of total alkaloids from two aspects:First, to observe the alkaloids of Solanum nigrum myeloma cell lines RPMI8226of pro-apoptotic role. Second, observe the effects of Solanum nigrum alkaloids on the expression of NF-kB, multiple myeloma, aimed at the molecular level initially revealed its anti-MM effect and mechanism of its in vivo anti-MM experiments provide an important experimental basis, developed with anti-MM effect of Chinese medicine drug preparation to establish the scientific basis.
Methods:The human myeloma RPMI-8226cells were object of study, the totalal kaloids of Solanum nigmm test object RPMI8226cells, NF-kB is the evaluation of AnnexinV-FITC/PI flowcytometry of RPMI8226tumor cell apoptosis;points of NF-kB expression to explore the role of Solanum nigrum alkaloids myeloma RPMI-8226cells apoptosis and NF-kB in immunofluorescencc staining.
Results:
1. In the25mg/L of Solanum nigrum total alkali processing RPMI8226cells48h in RPMI8226cells significantly inhibited the growth
2. Solatium nigrum total alkaloids12.5-25mg/L concentration range, significantly inhibited the growth of myeloma cells in RPMI-8226, and gradually increased as theconcentration increased and prolonged inhibition.
3. Drug concentration<25mg/L, induction of apoptosis is not obvious that the releaseof drug quality of50mg/L of early apoptosis increased significantly
4. When the drugconcentration of25mg/L (obvious) the apoptosis, NF-kB expressionin a lower level of statistical significance.
Conclusion:Solanum nigrum total alkaloids cytotoxicity in human multiple myeloma RPMI-8226cells were inhibit of RPMI-8226cells lines proliferation, promote cell apoptosis in a dose and time dependent. NF-kB expression levels in human multiple myeloma RPMI-8226cellline increases reduce the drug concentration with the total alkaloids o f Solanum nigrum.
目的：本研究以人骨髓瘤细胞株RPMI8226为研究对象,从两个方面观察龙葵总碱的作用：第一,观察龙葵总碱对骨髓瘤细胞株RPMI8226的促凋亡作用。第二,观察龙葵总碱对多发性骨髓瘤NF-κB表达的影响,旨在从分子水平初步揭示其抗MM的作用机制,为其进行体内抗MM实验提供重要的实验依据,为研制开发具有抗MM作用的中药新药制剂奠定科学基础。
方法：选用人骨髓瘤RPMI-8226细胞株为研究对象,以龙葵总碱为被试对象,采用MTT法检测细胞增殖活性,AnnexinV-FITC/P I双标记法分析细胞凋亡的改变；免疫荧光细胞化学染色分析NF-κ B的表达情况,探讨龙葵总碱对人骨髓瘤RPMI-8226细胞的凋亡作用以及对NF-κ B表达的影响。
结果：1.在25mg/L龙葵总碱处理RPMI-8226细胞48h后,RPMI8226细胞的生长出现明显的抑制作用,且随着浓度加大及时间延长,其抑制作用逐步增强。
2.药物浓度<25mg/L时,诱导凋亡作用不明显,当药物浓度达到25mg/L早期凋亡明显增多
3.当药物浓度达25mg/L(此时细胞凋亡明显)时,NFκ B表达水平的降低具有统计学意义。
结论：1.龙葵总碱可抑制人多发性骨髓瘤RPMI-8226细胞增殖,促进细胞凋亡,并且呈剂量和时间依赖性。2.NF-κ B表达量在人多发性骨髓瘤RPMI-8226细胞株随龙葵总碱的药物浓度增大而降低。
Solanum nigrum alkaloids myeloma cell apoptosis and apoptosis related genes of NF-kB
Objective:This study of human multiple myeloma cell strains RPMI8226, to observe the role of Solanum nigrum of total alkaloids from two aspects:First, to observe the alkaloids of Solanum nigrum myeloma cell lines RPMI8226of pro-apoptotic role. Second, observe the effects of Solanum nigrum alkaloids on the expression of NF-kB, multiple myeloma, aimed at the molecular level initially revealed its anti-MM effect and mechanism of its in vivo anti-MM experiments provide an important experimental basis, developed with anti-MM effect of Chinese medicine drug preparation to establish the scientific basis.
Methods:The human myeloma RPMI-8226cells were object of study, the totalal kaloids of Solanum nigmm test object RPMI8226cells, NF-kB is the evaluation of AnnexinV-FITC/PI flowcytometry of RPMI8226tumor cell apoptosis;points of NF-kB expression to explore the role of Solanum nigrum alkaloids myeloma RPMI-8226cells apoptosis and NF-kB in immunofluorescencc staining.
Results:
1. In the25mg/L of Solanum nigrum total alkali processing RPMI8226cells48h in RPMI8226cells significantly inhibited the growth
2. Solatium nigrum total alkaloids12.5-25mg/L concentration range, significantly inhibited the growth of myeloma cells in RPMI-8226, and gradually increased as theconcentration increased and prolonged inhibition.
3. Drug concentration<25mg/L, induction of apoptosis is not obvious that the releaseof drug quality of50mg/L of early apoptosis increased significantly
4. When the drugconcentration of25mg/L (obvious) the apoptosis, NF-kB expressionin a lower level of statistical significance.
Conclusion:Solanum nigrum total alkaloids cytotoxicity in human multiple myeloma RPMI-8226cells were inhibit of RPMI-8226cells lines proliferation, promote cell apoptosis in a dose and time dependent. NF-kB expression levels in human multiple myeloma RPMI-8226cellline increases reduce the drug concentration with the total alkaloids o f Solanum nigrum.
引文
[1]Giuliani N, Rizzoli V, Roodman GD. Multiple myeloma bone disease: Pathophysiology of osteoblast inhibition[J]. Blood,108(13): 3992-3996.
[2]Gilmore TD. Multiple myeloma:lust ing for NF-B.Cancer Cell[J],2007, 12(2):95-97
[3]马仰丽,侯健.骨髓瘤干/祖细胞是治疗多发性骨髓瘤的新靶标[J].中国实验血液学杂志2008年第16卷第6期,1459-1464
[A]Kumar SK, Ra jkumar SV, Dispenzierri A, et al. Improved survival in multiple myeloma and the impact of novel therapies[J]. Blood,2008, 111:2516-2520
[5]Alexanian R, Hant A, Khan D, et al. Treatment for multiple myeloma: Combination chemotherapy with different melphalan dose regimens [J]. JAMA,1969; 208:1680
[6]Alexanian R, Bonnet J, Gehan E, et al. Combination Chemotherapy for multiple myeloma [J]. Cancer,1972; 30:382
[7]Singhal S,Mehta J,Desikan R, et al. Anti tumor activity of thaiidomide in refratory multiple myeloma [J]. N Engi J Med,1999; 341 (21):1565-1571
[8]Palumbo A, Facon T, Sonneveld P, et al. Thaiidomide for treatment of multiple myeloma:10 years later [J]. Blood,2008; 111 (8):3968-3911
[9]ZemanvaM, Scud la V, Adam Z, et al. Low-dose Thalidomide regimens in therapy of relap sed or refractory multip le myeloma [J]. N epplsam a, 2008; 55 (4):345-349
[10]张晓黎,程骁赬,石晓菁.不同剂量沙利度胺对多发性骨髓瘤的疗效观察[J].湖南中医药大学学报2009年10月第29卷第10期60-61
[11]Thomas SK, Richards TA,WeberDM, et al. Lenalidomide in multiple myeloma [J]. Best Pract Res Clin Haem at ol,2007; 20 (4):717-735
[12]Rajkumar SV, Hayman SR, LacyMQ, et al. Combination therapywith lenalidomide p lus dexamethasone (Rev/Dex) for newly diagnosed myeloma [J]. Blood,2005,106 (13):4050-4053
[13]Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma[J]. N Engl J Med,2003, 348:2609-2617.
[14]Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma[J]. N Engl J Med,2005,352:2487-2498.
[29]san Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma [J]. N Engl J Med,2008,359:906-917.
[15]Markovina S, Cal landerNS, OConnor SL, et al. Bortezomib resistant nuclear factor-kappa B activity in Multip le myeloma cells [J]. M ol Cancer Res,2008; 6 (8) 1356-1364
[16]Park J, Ahn KS, Bae EK, et al. Blochage of interleukin 6 signaling with 6-amino-4-quinazoline synergistically induces the inhibitory effect of bortezomib in human U266 cells[J]. AnticancerD rugs,2008; 19 (8) 777-782
[17]Paramore A, Frants S. Bortezomib [J]. Nat Rev Drug Discov,2003,2: 611-612.
[18]赵瑜,靖域,薄剑,等PD与VAD方案对多发性骨髓瘤的疗效比较[J].中国实验血液学杂志2010；18(3)：652-654
[19]Santucci R,Mackley PA.Sebt S, et al. Farnesyltransferase inhibitors and their role in the treatment of multiple myeloma [J]. Cancer Control,2003,10:384
[20]Beaup re DM, Cepero E, Obeng EA, et al. R115777 induces Ras independent apop tosis of myeloma cells viamultip le intriusis pathways [J]. Mol Cancer Ther,2004; 3(2):179-186
[21]Alsina Ag,Fonseca R,Wilson EF, et al. The farnesyltransferase inhibitor zarnestra iswell tolerated, induces stabilization of disease and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma [J]. Blood,2004; 103 (9):3271-3277
[22]俞庆宏,战榕,黄豪博. 三氧化二砷对骨髓瘤细胞系U266抑制增殖及诱导凋亡的机制研究[J].中国实验血液学杂志,2007(5)：982-985.
[23]岳文彬,樊青霞,三氧化二砷、沙利度胺和地塞米松治疗复发性难治性多发性骨髓瘤[J].医药论坛杂志2010年9月第31卷第18期85-86.
[24]Han S, Wang B, Cotter M J, et al. Overcoming immune tolerance against multiple myeloma with lentiviral calnexin-engineered dendritic cell [J].Mol Ther,2008,16(2):269-279
[25]张梅,尹晓然,骆云雅,等.树突细胞介导的独特型瘤苗的体外抗骨髓瘤作用[J].中华血液学杂志,2005,26：593-597.
[26]陈佩,黄振翘老中医治疗多发性骨髓瘤临床经验黑龙江中医药2008,37(4)2
[27]任荣政,鞠立霞,周永明治疗多发性骨髓瘤经验[J].中医杂志2007年第23卷第2期306-308
[28]邹本宏刘宝文教授应用补阳还五汤治疗多发性骨髓瘤经验介绍[J].新中医2008年第40卷第2期
[29]戴媺,陈志雄.补肾法在血液病中的临床应用[J].医药论坛杂志2007,28(10)：121-122.
[30]刘琨,李达,张宏业.87例多发性骨髓瘤的中医证型分析[J].新中医,2007,39(8)：57.
[31]蒋楠,甘欣锦.中医辨治多发性骨髓瘤的体会[J].甘肃中医,200518(1)：7-8.
[32]王文暖,王文娜.辨证分型治疗多发性骨髓瘤13例疗效观察[J].河北中医,2010 32(7)：1104-1105.
[33]杜远升.博宁结合中药治疗63例肿瘤性骨溶解性骨破坏的临床研究医药产业资讯[J].2006,3(18)：11-13.
[34]陈健一,李晓惠,孔祥图.扶正解毒活血方合用亚砷酸注射液治疗难治性多发 性骨髓瘤30例[J].河北中医,2007,29(11)：1009-1010.
[35]张薇薇,杨新宇：复方苦参注射液联合化疗治疗多发性骨髓瘤的临床研究[J].湖南中医药大学学报,2010,30(3)：68-69.
[36]王蔚,陆道培.龙葵总提取物对多发性骨髓瘤U266细胞株的作用[J].北京大学学报(医学版),2005,37(3)：240.
[37]顾锦华,张伟,李锋,等.复方龙葵胶囊抗肿瘤作用及其对肿瘤细胞周期分布的影响[J].时珍围医国药,2006,17(12)：2463.
[38]罗文娟,王光辉.周新兰,等.螺甾皂苷类化合物的体外抗人肝癌细胞增殖作用[J].现代肿瘤医学,2007,15(3)：307.
[39]季宇彬,王胜惠,高世勇,等.龙葵总碱对H22荷瘤小鼠细胞膜流动性和膜蛋白水平的影响[J].中草药,2005,36(2)：239.
[40]季宇彬,王胜惠,高世勇,等.龙葵总碱对H22荷瘤小鼠肿瘤细胞膜唾液酸和封闭度的影响[J].中草药,2005,36(1)：79.
[41]季宇彬,王宏亮,高世勇.龙葵总碱对肿瘤细胞膜ATP酶活性的影响[J].哈尔滨商业大学学报(自然科学版),2005,21(2)：127.
[42]安磊,唐劲天,刘新民,等.龙葵抗肿瘤作用机制研究进展[J].中国中药杂志,2006,3I(15)：1125.
[43]季宇彬,王宏亮,高世勇.龙葵总碱对荷瘤小鼠肿瘤细胞DNA和RNA的影响[J].中草药,2005,36(8)：1200.
[44]Heo K S, Lee S J, Lim K T. Cytotoxic effect of glycoprotein isolated from Solanum nigrum L. through the inhibition of hydroxyl radical-induced DNA-binding activities of NF-kappa B in HT-29 cells [J]. Environ Toxicol Pharmacol,2004,17 (1):45.
[45]周健,吴远彬,蒋东霞,宋永平,魏旭东.人骨髓瘤细胞RPMI8226的生物学特性[J].肿瘤基础与临床,2010年6月第23卷第3期185-188
[1]戴嫩,陈志雄.补肾法在血液病中的临床应用[J].医药论坛杂志,2007,28(10)：121-122.
[2]刘琨,李达,张宏业.87例多发性骨髓瘤的中医证型分析[J].新中医,2007,39(8)：57.
[3]蒋楠,甘欣锦.中医辨治多发性骨髓瘤的体会[J].甘肃中医,200518(1)：7-8.
[4]王文暖,王文娜.辨证分型治疗多发性骨髓瘤13例疗效观察[J].河北中医,2010 32(7)：1104-1105.
[5]杨月艳.多发性骨髓瘤的中医辨治特点[J].中西中医,2008,24(1)：59-60.
[6]潘铭.中西医结合治疗多发性骨髓瘤21例疗效分析[J].中医药学报,2008,36(1)：72-73.
[7]唐伟兰,金碧琳,周梅,戴关荣,王晓英.中西医结合治疗多发性骨髓瘤25例疗效观察[J].浙江中医杂志2008,43(6)：.33 1
[8]苏凤哲.中医药治疗多发性骨髓瘤临床探讨[J].世界中西医结合杂志,2007, 2(9)：551.
[9]杜远升.博宁结合中药治疗63例肿瘤性骨溶解性骨破坏的临床研究医药产业资讯[J].2006,3(18)：11-13.
[10]董学斌,赵秀荣.补肾化瘀解毒方配合化疗治疗多发性骨瘤肾损害的临床观察[J].贵阳中医学院学报,2008,309(2)：37-39.
[11]陈健一,李晓惠,孔祥图.扶正解毒活血方合用亚砷酸注射液治疗难治性多发性骨髓瘤30例[J].河北中医,2007,29(11)：1009-1010.
[12]张薇薇,杨新宇.复方苦参注射液联合化疗治疗多发性骨髓瘤的临床研究[J].湖南中医药大学学报,2010,30(3)：68-69.
[13]唐庆.参芪扶正注射液配合VAD方案化疗治疗多发性骨髓瘤22例分析[J].肿瘤防治研究,2005,32(6)373.
[14]乔爱国.益肾活血法配合反应停治疗多发性骨髓瘤的疗效观察[J].辽宁中医杂志,2007,34(4)462-463.
[15]李宏良,曾荣香,田华琴,梁贵文,黄小青,陈学彰.华蟾素联合MPT方案治疗多发性骨髓瘤疗效观察[J].中华全科医学,2010,8(2)：169-171.
[2]Gilmore TD. Multiple myeloma:lust ing for NF-B.Cancer Cell[J],2007, 12(2):95-97
[3]马仰丽,侯健.骨髓瘤干/祖细胞是治疗多发性骨髓瘤的新靶标[J].中国实验血液学杂志2008年第16卷第6期,1459-1464
[A]Kumar SK, Ra jkumar SV, Dispenzierri A, et al. Improved survival in multiple myeloma and the impact of novel therapies[J]. Blood,2008, 111:2516-2520
[5]Alexanian R, Hant A, Khan D, et al. Treatment for multiple myeloma: Combination chemotherapy with different melphalan dose regimens [J]. JAMA,1969; 208:1680
[6]Alexanian R, Bonnet J, Gehan E, et al. Combination Chemotherapy for multiple myeloma [J]. Cancer,1972; 30:382
[7]Singhal S,Mehta J,Desikan R, et al. Anti tumor activity of thaiidomide in refratory multiple myeloma [J]. N Engi J Med,1999; 341 (21):1565-1571
[8]Palumbo A, Facon T, Sonneveld P, et al. Thaiidomide for treatment of multiple myeloma:10 years later [J]. Blood,2008; 111 (8):3968-3911
[9]ZemanvaM, Scud la V, Adam Z, et al. Low-dose Thalidomide regimens in therapy of relap sed or refractory multip le myeloma [J]. N epplsam a, 2008; 55 (4):345-349
[10]张晓黎,程骁赬,石晓菁.不同剂量沙利度胺对多发性骨髓瘤的疗效观察[J].湖南中医药大学学报2009年10月第29卷第10期60-61
[11]Thomas SK, Richards TA,WeberDM, et al. Lenalidomide in multiple myeloma [J]. Best Pract Res Clin Haem at ol,2007; 20 (4):717-735
[12]Rajkumar SV, Hayman SR, LacyMQ, et al. Combination therapywith lenalidomide p lus dexamethasone (Rev/Dex) for newly diagnosed myeloma [J]. Blood,2005,106 (13):4050-4053
[13]Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma[J]. N Engl J Med,2003, 348:2609-2617.
[14]Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma[J]. N Engl J Med,2005,352:2487-2498.
[29]san Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma [J]. N Engl J Med,2008,359:906-917.
[15]Markovina S, Cal landerNS, OConnor SL, et al. Bortezomib resistant nuclear factor-kappa B activity in Multip le myeloma cells [J]. M ol Cancer Res,2008; 6 (8) 1356-1364
[16]Park J, Ahn KS, Bae EK, et al. Blochage of interleukin 6 signaling with 6-amino-4-quinazoline synergistically induces the inhibitory effect of bortezomib in human U266 cells[J]. AnticancerD rugs,2008; 19 (8) 777-782
[17]Paramore A, Frants S. Bortezomib [J]. Nat Rev Drug Discov,2003,2: 611-612.
[18]赵瑜,靖域,薄剑,等PD与VAD方案对多发性骨髓瘤的疗效比较[J].中国实验血液学杂志2010；18(3)：652-654
[19]Santucci R,Mackley PA.Sebt S, et al. Farnesyltransferase inhibitors and their role in the treatment of multiple myeloma [J]. Cancer Control,2003,10:384
[20]Beaup re DM, Cepero E, Obeng EA, et al. R115777 induces Ras independent apop tosis of myeloma cells viamultip le intriusis pathways [J]. Mol Cancer Ther,2004; 3(2):179-186
[21]Alsina Ag,Fonseca R,Wilson EF, et al. The farnesyltransferase inhibitor zarnestra iswell tolerated, induces stabilization of disease and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma [J]. Blood,2004; 103 (9):3271-3277
[22]俞庆宏,战榕,黄豪博. 三氧化二砷对骨髓瘤细胞系U266抑制增殖及诱导凋亡的机制研究[J].中国实验血液学杂志,2007(5)：982-985.
[23]岳文彬,樊青霞,三氧化二砷、沙利度胺和地塞米松治疗复发性难治性多发性骨髓瘤[J].医药论坛杂志2010年9月第31卷第18期85-86.
[24]Han S, Wang B, Cotter M J, et al. Overcoming immune tolerance against multiple myeloma with lentiviral calnexin-engineered dendritic cell [J].Mol Ther,2008,16(2):269-279
[25]张梅,尹晓然,骆云雅,等.树突细胞介导的独特型瘤苗的体外抗骨髓瘤作用[J].中华血液学杂志,2005,26：593-597.
[26]陈佩,黄振翘老中医治疗多发性骨髓瘤临床经验黑龙江中医药2008,37(4)2
[27]任荣政,鞠立霞,周永明治疗多发性骨髓瘤经验[J].中医杂志2007年第23卷第2期306-308
[28]邹本宏刘宝文教授应用补阳还五汤治疗多发性骨髓瘤经验介绍[J].新中医2008年第40卷第2期
[29]戴媺,陈志雄.补肾法在血液病中的临床应用[J].医药论坛杂志2007,28(10)：121-122.
[30]刘琨,李达,张宏业.87例多发性骨髓瘤的中医证型分析[J].新中医,2007,39(8)：57.
[31]蒋楠,甘欣锦.中医辨治多发性骨髓瘤的体会[J].甘肃中医,200518(1)：7-8.
[32]王文暖,王文娜.辨证分型治疗多发性骨髓瘤13例疗效观察[J].河北中医,2010 32(7)：1104-1105.
[33]杜远升.博宁结合中药治疗63例肿瘤性骨溶解性骨破坏的临床研究医药产业资讯[J].2006,3(18)：11-13.
[34]陈健一,李晓惠,孔祥图.扶正解毒活血方合用亚砷酸注射液治疗难治性多发 性骨髓瘤30例[J].河北中医,2007,29(11)：1009-1010.
[35]张薇薇,杨新宇：复方苦参注射液联合化疗治疗多发性骨髓瘤的临床研究[J].湖南中医药大学学报,2010,30(3)：68-69.
[36]王蔚,陆道培.龙葵总提取物对多发性骨髓瘤U266细胞株的作用[J].北京大学学报(医学版),2005,37(3)：240.
[37]顾锦华,张伟,李锋,等.复方龙葵胶囊抗肿瘤作用及其对肿瘤细胞周期分布的影响[J].时珍围医国药,2006,17(12)：2463.
[38]罗文娟,王光辉.周新兰,等.螺甾皂苷类化合物的体外抗人肝癌细胞增殖作用[J].现代肿瘤医学,2007,15(3)：307.
[39]季宇彬,王胜惠,高世勇,等.龙葵总碱对H22荷瘤小鼠细胞膜流动性和膜蛋白水平的影响[J].中草药,2005,36(2)：239.
[40]季宇彬,王胜惠,高世勇,等.龙葵总碱对H22荷瘤小鼠肿瘤细胞膜唾液酸和封闭度的影响[J].中草药,2005,36(1)：79.
[41]季宇彬,王宏亮,高世勇.龙葵总碱对肿瘤细胞膜ATP酶活性的影响[J].哈尔滨商业大学学报(自然科学版),2005,21(2)：127.
[42]安磊,唐劲天,刘新民,等.龙葵抗肿瘤作用机制研究进展[J].中国中药杂志,2006,3I(15)：1125.
[43]季宇彬,王宏亮,高世勇.龙葵总碱对荷瘤小鼠肿瘤细胞DNA和RNA的影响[J].中草药,2005,36(8)：1200.
[44]Heo K S, Lee S J, Lim K T. Cytotoxic effect of glycoprotein isolated from Solanum nigrum L. through the inhibition of hydroxyl radical-induced DNA-binding activities of NF-kappa B in HT-29 cells [J]. Environ Toxicol Pharmacol,2004,17 (1):45.
[45]周健,吴远彬,蒋东霞,宋永平,魏旭东.人骨髓瘤细胞RPMI8226的生物学特性[J].肿瘤基础与临床,2010年6月第23卷第3期185-188
[1]戴嫩,陈志雄.补肾法在血液病中的临床应用[J].医药论坛杂志,2007,28(10)：121-122.
[2]刘琨,李达,张宏业.87例多发性骨髓瘤的中医证型分析[J].新中医,2007,39(8)：57.
[3]蒋楠,甘欣锦.中医辨治多发性骨髓瘤的体会[J].甘肃中医,200518(1)：7-8.
[4]王文暖,王文娜.辨证分型治疗多发性骨髓瘤13例疗效观察[J].河北中医,2010 32(7)：1104-1105.
[5]杨月艳.多发性骨髓瘤的中医辨治特点[J].中西中医,2008,24(1)：59-60.
[6]潘铭.中西医结合治疗多发性骨髓瘤21例疗效分析[J].中医药学报,2008,36(1)：72-73.
[7]唐伟兰,金碧琳,周梅,戴关荣,王晓英.中西医结合治疗多发性骨髓瘤25例疗效观察[J].浙江中医杂志2008,43(6)：.33 1
[8]苏凤哲.中医药治疗多发性骨髓瘤临床探讨[J].世界中西医结合杂志,2007, 2(9)：551.
[9]杜远升.博宁结合中药治疗63例肿瘤性骨溶解性骨破坏的临床研究医药产业资讯[J].2006,3(18)：11-13.
[10]董学斌,赵秀荣.补肾化瘀解毒方配合化疗治疗多发性骨瘤肾损害的临床观察[J].贵阳中医学院学报,2008,309(2)：37-39.
[11]陈健一,李晓惠,孔祥图.扶正解毒活血方合用亚砷酸注射液治疗难治性多发性骨髓瘤30例[J].河北中医,2007,29(11)：1009-1010.
[12]张薇薇,杨新宇.复方苦参注射液联合化疗治疗多发性骨髓瘤的临床研究[J].湖南中医药大学学报,2010,30(3)：68-69.
[13]唐庆.参芪扶正注射液配合VAD方案化疗治疗多发性骨髓瘤22例分析[J].肿瘤防治研究,2005,32(6)373.
[14]乔爱国.益肾活血法配合反应停治疗多发性骨髓瘤的疗效观察[J].辽宁中医杂志,2007,34(4)462-463.
[15]李宏良,曾荣香,田华琴,梁贵文,黄小青,陈学彰.华蟾素联合MPT方案治疗多发性骨髓瘤疗效观察[J].中华全科医学,2010,8(2)：169-171.