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研究生(外文):Chiao-Lin Yen
論文名稱(外文):Investigation of the Therapeutic Efficacy of Antitumor Nanodrug Combined with Curcumin and Hyperthermia
外文關鍵詞:nanodrughyperthermiacurcumincancer treatment
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薑黃素(curcumin)具有優異的抗氧化、抗發炎等功效,而根據文獻記載,其也有抑制腫瘤生長與轉移的潛力。本研究使用小鼠耳朵腫瘤模式探討奈米抗癌藥物pegylated liposomal doxorubicin (PLD)結合薑黃素和熱治療三者對於腫瘤治療是否有加成的抗癌效果。
本研究使用小鼠耳朵腫瘤模式(Mouse Ear Tumor Model),每隻Balb/c雄鼠左右耳皆植有結腸直腸腺癌CT-26細胞,並於腫瘤長至約50 mm3 開始治療(約接種後10至12天)。實驗共分10個實驗組:控制組、Sham組、Heat組、Curcumin組、PLD組、PLD+Heat+Cur組、PLD+Cur組、PLD+Heat組、Heat+Cur組和Heat+DMSO組。其中奈米抗癌藥物一律經由尾靜脈注射,每週施打一次,劑量為每公斤6毫克,總共治療三次;薑黃素則直接注射於腫瘤組織,劑量為每公斤30毫克,熱治療則是將腫瘤浸泡於43.5℃的溫水浴15分鐘;薑黃素和熱治療則分為不給予或每週給予兩次,治療一共六次。

Curcumin, a natural derivative from Curcumin longa, known for its outstanding antioxidant and anti-inflammatory capabilities, has recently drawn the attention of cancer researchers, showing its ability to inhibit the growth and metastasis of tumors. In the present study, we investigated whether a combination of anticancer nanodrug pegylated liposomal doxorubicin (PLD), curcumin and hyperthermia would have a synergistic antitumor effect in mouse ear tumor model.
In this study, each male Balb/c mouse received implantation of colorectal adenocarcinoma CT-26 cells on both ears. Treatments started whenever tumors grew up to about 50 mm3 (10 to 12 days after tumor cell inoculation). Experiments comprised ten groups:Control, Sham, Hyperthermia only, Curcumin only, PLD only, PLD with curcumin and hyperthermia, PLD with curcumin, PLD with hyperthermia, Hyperthermia with curcumin and Hyperthermia with DMSO. PLD was injected once every week through the tail vein with a dosage of 6 mg/kg, whereas curcumin was administered intratumorally twice a week at the dosage of 30 mg/kg. Semiweekly, tumor tissue was heated to 43.5°C in a water bath for 15 minutes. The above mentioned therapies took three weeks long.
The experiment results showed that PLD+HT+Cur, PLD, PLD+HT were the three groups which demonstrated the best treatment efficacy. Furthermore, PLD or PLD+Cur combined with hyperthermia had better curative effect than without hyperthermia. The present study proved that PLD combined with curcumin and hyperthermia was more effective than PLD alone, and that hyperthermia is able to increase the sensitivity of tumor cells to anticancer drugs. Moreover, curcumin exhibited a great adjuvant effect when combined with hyperthermia to suppress the growth of tumor. However, this wasn''t observed in the PLD+Cur group, which might be the result of the overdose of PLD. Hence, in the future, the dosage of PLD should be lowered, in order to investigate the antitumor efficacy of curcumin.

口試委員會審定書 i
致謝 ii
中文摘要 iv
Abstract v
目次 vii
圖目錄 ix
表目錄 xi
第一章 緒論 1
1.1 腫瘤生成 1
1.2 血管新生 3
1.3 癌症治療 3
1.4 奈米抗癌藥物 4
1.5 薑黃素 5
1.6 熱治療 6
1.7 研究動機與目的 7
第二章 材料與方法 9
2.1 實驗動物 9
2.2 腫瘤細胞株 9
2.3 小鼠耳朵模式 9
2.4 奈米抗癌藥物 10
2.5 薑黃素 10
2.6 熱治療 11
2.7 數值統計與分析方法 11
2.8 實驗設計與流程 12
第三章 結果與討論 15
3.1 控制組和Sham組之比較 15
3.2 Cur組和Heat組之比較 17
3.3 PLD+Cur組和PLD+Heat組之比較 19
3.4 PLD組和PLD+Heat+Cur組之比較 21
3.5 Heat+DMSO組和Heat+Cur組之比較 23
3.6 PLD搭配薑黃素對腫瘤之治療 25
3.7 熱治療搭配薑黃素對腫瘤之治療 26
3.8 PLD搭配薑黃素結合熱治療對腫瘤之治療 28
3.9 各組小鼠體重變化情形 29
第四章 結論與未來展望 31
文獻資料 33

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