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Antitumor activity and associated mechanisms of Huachansu in cancer 华蟾素抗肿瘤活性及其相关机制

Antitumor activity and associated mechanisms of Huachansu in cancer 华蟾素抗肿瘤活性及其相关机制. Chemical Components of HuaChanSu 华蟾素化学成分. Indole Alkaloids 吲哚生物碱 : Serotonin 5- 羟色胺 Bufotenine 蟾毒色胺 Bufotenidine N- 三甲基 -5- 羟色胺 Cinobufotenine 华蟾毒色胺

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Antitumor activity and associated mechanisms of Huachansu in cancer 华蟾素抗肿瘤活性及其相关机制

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  1. Antitumor activity and associated mechanisms of Huachansu in cancer华蟾素抗肿瘤活性及其相关机制

  2. Chemical Components of HuaChanSu华蟾素化学成分 • Indole Alkaloids 吲哚生物碱: • Serotonin 5-羟色胺 • Bufotenine 蟾毒色胺 • Bufotenidine N-三甲基-5-羟色胺 • Cinobufotenine 华蟾毒色胺 • Steroidal cardiac glycosides–Bufadienolides 甾体强心甙: • Bufolin 蟾毒灵 • Resibufogenin 脂蟾毒配基 • Cinobufagin 华蟾毒配基 • Marinobufagin 南美蟾蜍毒素 • bufotalin蟾毒苷 The antitumor activity of HuaChanSu may be attributed to bufadienolides. 华蟾素的抗肿瘤活性可能因蟾毒甾体强心甙类引起。

  3. Effect of Huachansu and cardiac glycosides on Proliferation of Various Human Cancer Cells （华蟾素对不同人肿瘤细胞增殖的影响）

  4. 华蟾素的抗瘤活性与Na,K-ATPase相关

  5. Characterization ofNa,K-ATPase • Na,K-ATPase typically occurs as a heterodimer with one  and one  subunits （Na,K-ATP酶多以二聚体形式出现，包括一个和一个亚单位） •  subunits consist of multi-scanning transmembrane proteins with catalytic activity and have binding sites for ATP and cardiac glycosides; four  forms have been identified （  亚单位包括具有催化活性的跨膜蛋白以及ATP和强心甙类的结合位点，已有四种异构体被确定） •  2 and  3 isoforms are 250-fold more sensitive to cardiac glycosides compared to the 1 isoform. （ 2和 3异构体对强心甙的敏感性是1的的250倍 ） • Studies have suggested that human tumor Hela cells are much more sensitive to ouabain than rodent cells (3T3 and CHO cells) （研究提示Hela细胞对喹巴因的敏感性明显高于鼠类细胞，如3T3和CHO细胞） • Na, K-ATPase  3 isoform is up-regulated in human colorectal cancer (as cells move from normal to malignant phenotype they become better targets for Rx with cardiac glycosides) （ Na,K-ATP酶 3 异构体在人肠癌中表达上调，在正常细胞发生恶性转化时，可作为强心甙治疗的作用靶点）

  6. Human Pancreatic Cancer Panc-1 Cells are More Sensitive to Huachansu Treatment Than are BxPC3 Cells（人胰腺癌细胞panc-1对华蟾素的敏感性明显高于BxPC3细胞）

  7. Huachansu Induces G2/M Arrest in PANC-1 Cells, whereas a G1 Arrest or Apoptosis in BxPC3 Cells（在panc-1细胞中，华蟾素诱导G2/M期阻滞，但在BxPC3细胞则是诱导G1期阻滞和细胞调亡） BxPC3 cells PANC-1 cells

  8. Huachansu Inhibits PANC-1 Xenograft Growth More Strongly Than That of BxPC3（华蟾素对panc-1移植瘤生长的抑制作用强于对BxPC3的作用 ） PANC-1 BxPC3  1  3

  9. Synergistic Effect of Huachansu and Gemcitabine against Pancreatic Cancer（华蟾素和吉西他滨治疗胰腺癌的协同作用） BxPC3 cells PANC-1 cells

  10. Huachansu Augments the Antitumor Activity of Gemcitabine in BxPC3 Xenograft Model（华蟾素增加了吉西他滨对BxPC3移植瘤的抑瘤活性） PANC-1 BxPC3

  11. Evaluation of Effect of Huachansu or Bufalin as A Single Agent or Combination of Sorafenib in Human Hepartcellular Carcinoma 华蟾素联合索拉非尼治疗肝癌

  12. Huachansu augments the anti-proliferative effect of sorafenib in Hep3G cells Hep3G cell PLC/PRF/5 cell

  13. A549 H460 HCS 24h Control No IR 2Gy 4h Huachansu exerts remarkable radiosensitizative effect in human non-small cell lung cancer cells Control HCS 24h

  14. Anticancer activity of Huachansu on Non-Hodgkin Lymphoma 华蟾素对非霍奇金淋巴瘤的抗瘤作用

  15. Huachansu effectively inhibited proliferation of non-Hodgkin lymphoma Raji and Ramos cells

  16. Huachansu inhibited proliferation of non-Hodgkins by induction of apoptosis 1=0 unit 2=0.5 unit 3=2.5 unit 4=0 unit 5=0.5 unit 6=2.5 unit Rajis Ramos Annexin V staining

  17. 小 结 • 华蟾素可增加化闻敏感性 • 华蟾素可增加化疗敏感性 • 华蟾素的抗瘤作用与对Na,K-ATPase的抑制相关

  18. Thank you !

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