鍵結體抑素類似物之微脂粒斑蝥素並於高壓氧環境對於乳癌之治療與評估

Evaluation of Octreotide-Conjugated Liposomal Cantharidin in Hyperbaric Oxygen Environment Treating for Breast Cancer

張智翔(Chih-Hsiang Chang)

指導教授 ： 劉得任

臺北醫學大學/口腔醫學院/生物醫學材料研究所/碩士(2006年)

摘要

微脂粒應用在癌症化學治療上有許多的研究，並且有少數上市的產品。因此，具標靶的微脂粒配方化療藥物還是值得研究。
在此研究，設計標靶微脂粒，在表面鍵結體抑素的類似物，Octreotide，利用其和特定腫瘤細胞有專一性結合的特性，並且引起胞飲作用，增加藥物進入腫瘤，增加藥效。
當高壓氧造成血管及細胞增生使腫瘤組織血流量增加，使到達腫瘤的藥物量增加。當細胞受氧刺激活化後，胞吞藥物增加。當高壓氧展現抑制乳癌細胞、血管增生時，也視為輔助化療藥物的效果。
斑蝥素在細胞實驗中有明顯抗癌的功能。但是應用在動物實驗中，面臨了高劑量易致死，低劑量無效的問題。因此，在動物實驗中，將斑蝥素包覆在微脂粒中，成功克服易致死的問題，並且發現明顯減少腫瘤體積。
「高壓氧」及「Octreotide鍵結微脂粒」，的確增加斑蝥素的細胞毒性。
微脂粒配方的斑蝥素克服斑蝥素的體內毒性，並且明顯降低腫瘤體積。

關鍵字

微脂粒 ； 體抑素 ； 腫瘤 ； 高壓氧 ； 斑蝥素

並列摘要

There were a lot of well developments liposomal drugs. And really have some clinically approved products. Now, we are keeping studying in targeted-liposome and it has great potential.
In this study, we design targeted-liposome, which conjugated a somatostatin analog, Octreotide, used for specific receptor targeting of tumors. And which can induce endocytosis of cells. Thus, more doses can enter the tumor cell.
When HBO promote cell proliferation and angiogensis, it may result in more drugs reach the tumor tissue. When HBO promote the proliferation of cell, it may result in more drugs uptake by cells. When HBO inhibit cell proliferation and angiogensis, it may see as enhance chemotherapy.
Cantharidin do cause tumor cell death in cell culture experiment. But, in animal experiment, many researchers face the problem: High concentration of drugs cause animals die. Low concentration of drugs has no effect. We use PEG-liposomal CAN really overcome these problem. Using our formula, we rare cause animals die and do decrease the tumor size.
HBO and Octreotide-conjugated liposome do enhance the cytotoxicity of cantharidin.
PEG-liposomal CAN do overcome the toxicity in vivo. And reduce the tumor size dramatically.

並列關鍵字

liposome ； somatostatin ； tumor ； hyperbaric oxygen ； cantharidin

參考文獻

iatrogenic cerebral arterial gas embolism. Undersea Hyperb Med

[31] Ganguly BJ, Tonomura N, Benson RM, Osborne BA, Granowitz

polyethyleneglycols effectively prolong the circulation time of

liposomes. FEBS Lett 1990 Jul 30;268(1):235-7.

[3] Blume G, Cevc G. Molecular mechanism of the lipid vesicle