以薑黃素微胞搭配奈米抗癌藥物對腫瘤療效之探討

Investigation of the Therapeutic Efficacy of Antitumor Nanodrug Combined with Curcumin Micelles

姚秉瑜(Bing-Yu Yao)

指導教授 ： 林文澧

國立臺灣大學/工學院/醫學工程學研究所/碩士(2014年)

https://doi.org/10.6342/NTU.2014.00127

摘要

摘要
研究目的:
探討能否藉由Liposomal Doxorubicin搭配奈米薑黃素微胞來增加對腫瘤治療之療效並降低化療對小鼠之副作用。
材料與方法:
本實驗使用之實驗小鼠為周齡4~5周，體重20~22公克Balb/c雄鼠，將小鼠結腸直腸癌細胞(Murine Colorectal Adenocarcinoma) CT-26植入小鼠兩側耳朵皮下。利用電子式游標尺測量腫瘤體積，拍照紀錄並利用電子天平測量小鼠體重。在植入腫瘤後第10天開始治療，腫瘤治療之起始體積為50mm3。
實驗設計組包括: Control組、Free Curcumin(20mg/kg)組、Curcumin Micelles Low Dose(20mg/kg)(CUM20)組、Curcumin Micelles High Dose(40mg/kg)(CUM40)組、PLD Low Dose(4mg/kg)(PLD4)組、PLD High Dose(6mg/kg)(PLD6)組、CUM20+ PLD 6組以及CUM40 + PLD4組。
實驗結果:
單以Curcumin治療不論高劑量(40mg/kg)、低劑量(20mg/kg)以及Free Cucumin(20mg/kg)治療在療程結束後腫瘤體積皆較Control組小並有顯著差異。而高劑量PLD(6mg/kg)搭配Curcumin治療與單用高劑量PLD(6mg/kg)之間在第22天之後開始出現統計上的顯著差異。低劑量PLD(4mg/kg) 搭配Curcumin(40mg/kg)治療與單用高劑量PLD(6mg/kg)其療程結束後抑制腫瘤生長的情況相仿，並且降低對體重下降的副作用。此外，薑黃素在腫瘤組織內的定量包覆成微胞的形式的薑黃素能夠增加其在腫瘤組織內的累積量。

關鍵字: 薑黃素、奈米藥物、癌症治療

關鍵字

薑黃素 ； 奈米藥物 ； 癌症治療

並列摘要

ABSTRACT
In this study, we investigated whether liposomal doxorubicin combined with curcumin micelles would have synergistic antitumor effect and decrease the chemotherapy side effect on mice.
Male Balb/c mice weighing from 19~22g were used in this study, each mouse received subcutaneous implantation of murine colorectal adenocarcinoma CT-26 cells in both ears. The treatments were initialed on Day 10 when the tumor volumes were about 50mm3. Tumor volumes were measured every three days through Day 28 using digital calipers and the body weights were monitored.
Experiments comprised eight groups: Control, Free curcumin(20mg/kg), curcumin micelles low dose(20mg/kg)(CUM20), curcumin micelles high dose(40mg/kg)(CUM40), PLD low dose(4mg/kg)(PLD4), PLD high dose(6mg/kg)(PLD6), PLD6 with CUM20 and PLD4 with CUM40.
The results showed that curcumin micelles increased more curcumin accumulation in tumor tissue than free curcumin. Tumor volumes treated with free curcumin, CUM20, and CUM40 were significantly smaller than control after 22 day. The present study showed that PLD6 combined with curcumin micelles was more effective than PLD6 alone. Furthermore, tumor growth in group treated with PLD4 combined with CUM40 was similar to that in group treated with PLD6 alone, but it eased the adverse effect caused by PLD chemotherapy.

並列關鍵字

curcumin ； nanodrug ； cancer treatment

參考文獻

論文，國立陽明大學傳統醫藥研究所。

[1] Bae, Y. H. and K. Park., "Targeted drug delivery to tumors: myths, reality and possibility." J Control Release. 2011; 153(3): 198-205.

[2] Binion, D. G., et al., "Curcumin inhibits VEGF-mediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition." Gut 2008; 57(11): 1509-1517.

[3] Fukuda, T., et al. "Pegylated liposomal doxorubicin for platinum-resistant or refractory Mullerian carcinoma (epithelial ovarian carcinoma, primary carcinoma of Fallopian tube and peritoneal carcinoma): A single-institutional experience." Oncol. Lett. 2013; 5(1): 35-38.

[4] Gong, C., et al., "Improving antiangiogenesis and anti-tumor activity of curcumin by biodegradable polymeric micelles." Biomaterials 2013; 34(4): 1413-1432.