天然抗氧化剂对光动力疗法的影响
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摘要
光动力疗法(PhotodynamicTherapy, PDT)是基于在癌细胞中产生过多的活性氧杀伤肿瘤细胞的一种癌症治疗方法。该疗法借助某些特定药物(光敏剂)进入患者体内后,动态聚集于肿瘤细胞中。在一定波长光照射下光敏剂发生光敏化反应产生单线态氧等活性氧导致生物大分子氧化损伤,并由此造成细胞器损伤进而破坏肿瘤组织。直接和间接的证据都表明虽然多种活性氧参与其中,但是单线态氧对肿瘤细胞的杀伤起着决定性的作用。
目前许多癌症患者在常规治疗的同时也会结合一些辅助治疗。许多具有抗氧化性的天然植物成分被认为是安全和健康的食品,其中有许多因被认为对癌症的防治有益已广泛应用于制药、保健品等领域。必须注意到的是许多治疗癌症策略本身就是基于在癌细胞中产生过多的活性氧进而将其杀死的,所以具有抗氧化性的物质在降低癌症治疗毒性的同时可能潜在的降低癌症治疗效率。本文就天然抗氧化物对光动力疗法的影响进行了具体深入的研究。
本论文所完成的主要工作是：研究了不同光源对光动力疗法效率的影响以及光动力中不同光源的最佳光剂量并使用最佳的光源条件研究了鞣花酸、染料木素、刺芒柄花素、大豆甙元、α-山竹黄酮和γ-山竹黄酮这几种天然抗氧化物对光动力疗法的影响。
本文主要结论如下：
1.染料木素抑制了K562细胞的生长,增加了光动力疗法对K562细胞的杀伤(24小时孵育)以及光动力处理中细胞膜的氧化损伤和细胞的凋亡(12小时孵育)。
2.大豆甙元抑制了K562细胞的生长。大豆甙元没有增加光动力疗法对K562细胞的杀伤,也没有增加光动力处理中细胞膜的氧化损伤和细胞的凋亡(24小时孵育)。
3.刺芒柄花素没有抑制K562细胞的生长。但其增加了光动力疗法对K562细胞的杀伤以及光动力处理中细胞膜的氧化损伤和细胞的凋亡(12小时孵育)。
4.鞣花酸抑制了K562细胞的生长,100μM的鞣花酸可以增加光动力疗法对K562细胞的杀伤以及光动力处理中细胞膜的氧化损伤和细胞的凋亡(12小时孵育)。
5.山竹黄酮抑制了K562细胞的生长,增加光动力疗法对K562细胞的杀伤以及光动力处理中细胞膜的氧化损伤和细胞的凋亡(12小时孵育)。α-山竹黄酮对细胞的生长抑制和对光动力的增强效果都比γ-山竹黄酮强。
6.提示抗氧化剂对光动力疗法的影响很可能决定于对单线态氧的清除能力。
论文主要创新点：
1.本文首次研究了食物中含有的天然抗氧化剂在癌症治疗中应用时对光动力疗法的影响。目前还没有研究小组将抗氧化剂在癌症治疗中的应用同其对光动力疗法的影响结合起来研究。仅有少数研究小组研究了具有抗氧化性的药物对光动力的影响,其中并没有注意到食物的天然抗氧化性也没有注意到多种抗氧化剂的比较以及相互差别的分析。
2.本文首次提出抗氧化剂对光动力疗法的影响很可能决定于对单线态氧的清除能力。由于实验结果的缺乏,目前关于抗氧化性物质是否有益于光动力治疗还是个有争论的话题。本文研究提示抗氧化剂是否有益于光动力治疗可能取决于其对单线态氧的清除能力。
3.本文首次发现多种天然抗氧化剂对光动力疗法有增强作用。本文发现：鞣花酸、染料木素、刺芒柄花素、α-山竹黄酮和γ-山竹黄酮在体外培养细胞体系中可以加强光动力的效果。
Photodynamic therapy (PDT) is a treatment for cancer and certain non-malignant pathologies that is generally characterized by overgrowth of unwanted or abnormal cells. It includes loading of the target cells with a photosensitizer and subsequent illumination with visible light. When the oxygen existence, the combination of light and photosensitizer causes generation of reactive oxygen species (ROS), in particular singlet oxygen, superoxide anion and hydroxyl radical, resulting in target cell death either through necrosis or apoptosis. Direct and indirect evidence supports a prevalent role for singlet oxygen in the molecular processes initiated by PDT.
Natural antioxidants have antioxidant properties and it was popular in diet and medicine. Owing to natural antioxidants were potential anticancer drug, PDT and natural antioxidants were likely use in cancer therapy at same time. It must be noticed that any antioxidant found to reduce toxicity of tumor therapy on healthy tissue has the potential to decrease effectiveness of cancer therapy on malignant cells. Therefore, study the influence of natural antioxidants on PDT is very significant.This research mainly studies the influence of natural antioxidants on PDT.
Conclusions got from experiments as follows:
1. Genistein inhibits K562 cells proliferation. Supplementation of genistein in K562 cells increases the lipid peroxidation, DNA damage, and decreases the survival rate in PDT treatment.
2. Daidzein inhibits K562 cells proliferation. It couldn't increase cells death, the lipid peroxidation and cell apoptosis in ALA-PDT.
3. Formononetin couldn't inhibit K562 cells proliferation. Supplementation of formononetin in K562 cells increases the lipid peroxidation, DNA damage, and decreases the survival rate in PDT treatment.
4. Ellagic acid inhibits K562 cells proliferation. Supplementation of 1OOμM ellagic acid in K562 cells increases the lipid peroxidation, DNA damage, and decreases the survival rate in PDT treatment.
5. Mangostin inhibits K562 cells proliferation. It enhanced cells death after incubating 24h in a dose-dependent manner when undergoing PDT treatment. Supplementation of mangostin in K562 cells increases the lipid peroxidation, DNA damage, and decreases the survival rate after incubating 24h in PDT treatment.
6. These results implied that the effect of antioxidants on PDT may depend on its sensitization ability to singlet oxygen. The innovations of the dissertation:
The combine of the effects of anti-oxidant in cancer therapy and PDT was not be studied by any researcher. The present paper studied this firstly.
目前许多癌症患者在常规治疗的同时也会结合一些辅助治疗。许多具有抗氧化性的天然植物成分被认为是安全和健康的食品,其中有许多因被认为对癌症的防治有益已广泛应用于制药、保健品等领域。必须注意到的是许多治疗癌症策略本身就是基于在癌细胞中产生过多的活性氧进而将其杀死的,所以具有抗氧化性的物质在降低癌症治疗毒性的同时可能潜在的降低癌症治疗效率。本文就天然抗氧化物对光动力疗法的影响进行了具体深入的研究。
本论文所完成的主要工作是：研究了不同光源对光动力疗法效率的影响以及光动力中不同光源的最佳光剂量并使用最佳的光源条件研究了鞣花酸、染料木素、刺芒柄花素、大豆甙元、α-山竹黄酮和γ-山竹黄酮这几种天然抗氧化物对光动力疗法的影响。
本文主要结论如下：
1.染料木素抑制了K562细胞的生长,增加了光动力疗法对K562细胞的杀伤(24小时孵育)以及光动力处理中细胞膜的氧化损伤和细胞的凋亡(12小时孵育)。
2.大豆甙元抑制了K562细胞的生长。大豆甙元没有增加光动力疗法对K562细胞的杀伤,也没有增加光动力处理中细胞膜的氧化损伤和细胞的凋亡(24小时孵育)。
3.刺芒柄花素没有抑制K562细胞的生长。但其增加了光动力疗法对K562细胞的杀伤以及光动力处理中细胞膜的氧化损伤和细胞的凋亡(12小时孵育)。
4.鞣花酸抑制了K562细胞的生长,100μM的鞣花酸可以增加光动力疗法对K562细胞的杀伤以及光动力处理中细胞膜的氧化损伤和细胞的凋亡(12小时孵育)。
5.山竹黄酮抑制了K562细胞的生长,增加光动力疗法对K562细胞的杀伤以及光动力处理中细胞膜的氧化损伤和细胞的凋亡(12小时孵育)。α-山竹黄酮对细胞的生长抑制和对光动力的增强效果都比γ-山竹黄酮强。
6.提示抗氧化剂对光动力疗法的影响很可能决定于对单线态氧的清除能力。
论文主要创新点：
1.本文首次研究了食物中含有的天然抗氧化剂在癌症治疗中应用时对光动力疗法的影响。目前还没有研究小组将抗氧化剂在癌症治疗中的应用同其对光动力疗法的影响结合起来研究。仅有少数研究小组研究了具有抗氧化性的药物对光动力的影响,其中并没有注意到食物的天然抗氧化性也没有注意到多种抗氧化剂的比较以及相互差别的分析。
2.本文首次提出抗氧化剂对光动力疗法的影响很可能决定于对单线态氧的清除能力。由于实验结果的缺乏,目前关于抗氧化性物质是否有益于光动力治疗还是个有争论的话题。本文研究提示抗氧化剂是否有益于光动力治疗可能取决于其对单线态氧的清除能力。
3.本文首次发现多种天然抗氧化剂对光动力疗法有增强作用。本文发现：鞣花酸、染料木素、刺芒柄花素、α-山竹黄酮和γ-山竹黄酮在体外培养细胞体系中可以加强光动力的效果。
Photodynamic therapy (PDT) is a treatment for cancer and certain non-malignant pathologies that is generally characterized by overgrowth of unwanted or abnormal cells. It includes loading of the target cells with a photosensitizer and subsequent illumination with visible light. When the oxygen existence, the combination of light and photosensitizer causes generation of reactive oxygen species (ROS), in particular singlet oxygen, superoxide anion and hydroxyl radical, resulting in target cell death either through necrosis or apoptosis. Direct and indirect evidence supports a prevalent role for singlet oxygen in the molecular processes initiated by PDT.
Natural antioxidants have antioxidant properties and it was popular in diet and medicine. Owing to natural antioxidants were potential anticancer drug, PDT and natural antioxidants were likely use in cancer therapy at same time. It must be noticed that any antioxidant found to reduce toxicity of tumor therapy on healthy tissue has the potential to decrease effectiveness of cancer therapy on malignant cells. Therefore, study the influence of natural antioxidants on PDT is very significant.This research mainly studies the influence of natural antioxidants on PDT.
Conclusions got from experiments as follows:
1. Genistein inhibits K562 cells proliferation. Supplementation of genistein in K562 cells increases the lipid peroxidation, DNA damage, and decreases the survival rate in PDT treatment.
2. Daidzein inhibits K562 cells proliferation. It couldn't increase cells death, the lipid peroxidation and cell apoptosis in ALA-PDT.
3. Formononetin couldn't inhibit K562 cells proliferation. Supplementation of formononetin in K562 cells increases the lipid peroxidation, DNA damage, and decreases the survival rate in PDT treatment.
4. Ellagic acid inhibits K562 cells proliferation. Supplementation of 1OOμM ellagic acid in K562 cells increases the lipid peroxidation, DNA damage, and decreases the survival rate in PDT treatment.
5. Mangostin inhibits K562 cells proliferation. It enhanced cells death after incubating 24h in a dose-dependent manner when undergoing PDT treatment. Supplementation of mangostin in K562 cells increases the lipid peroxidation, DNA damage, and decreases the survival rate after incubating 24h in PDT treatment.
6. These results implied that the effect of antioxidants on PDT may depend on its sensitization ability to singlet oxygen. The innovations of the dissertation:
The combine of the effects of anti-oxidant in cancer therapy and PDT was not be studied by any researcher. The present paper studied this firstly.
引文
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