奈米抗癌藥物搭配薑黃素和熱治療對腫瘤療效之探討

Abstract

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。 從實驗結果觀察到抑制腫瘤生長效果最好的三組分別是：PLD+Heat+Cur組、PLD+Heat組和PLD組，三組治療後最終腫瘤體積皆低於治療起始之腫瘤體積。此外，我們也發現當PLD組和PLD+Cur組這兩組加上熱治療後，會比原先沒有熱治療有更好的治療效果，但PLD組和PLD+Cur組相比並無顯著差異存在。另一方面，Heat+Cur組的腫瘤生長也較Heat組腫瘤緩慢，可見熱治療搭配薑黃素比只單獨使用熱治療有更好的腫瘤抑制效果。本研究證明了PLD搭配薑黃素和熱治療的療效優於單獨使用PLD的療效，且在治療中加入熱治療能提高腫瘤對抗癌藥物的敏感度。而在熱治療搭配薑黃素的療程中可以看見薑黃素的輔助效果，但PLD搭配薑黃素卻和單獨給予PLD兩組間卻無顯著差異，應是因為奈米抗癌藥物劑量過高，而無法彰顯出薑黃素的抗癌效果，未來應降低PLD的劑量，以探討其是否能加強PLD的療效。

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.