地瓜葉及其萃出物增強cisplatin對肺腺癌A549細胞生長的抑制作用:體外與體內研究

Sweet potato leaves and its extract enhance the growth inhibition effect of cisplatin on lung carcinoma A549 cells: in vitro and in vivo study

莊喻荏(Yu-Ren Zhuang)

指導教授 ： 葉姝蘭

中山醫學大學/健康管理學院/營養學研究所/碩士(2017年)

摘要

Cis-diammine-dichloro-platinum(II)(CDDP；cisplatin)目前在臨床廣泛被應用於治療多種癌症，但現今許多研究已證實CDDP會造成許多副作用，而限制其使用劑量。Quercetin (Q)屬於類黃酮，研究顯示具有抗腫瘤潛力，而在我們先前的預試驗檢不同蔬菜中Q的含量，結果顯示富含多種植化素的地瓜葉中Q含量最高，因此本研究分兩部分，第一為探討地瓜葉及其萃出物在體內是否能增強CDDP抗癌效果。第二為探討地瓜葉萃出物中的植化素包含，CY、CH、CA在體外是否具有增強CDDP抑制A549 細胞生長的效果。
第一部分
本研究利用異種移植(Xenotransplantation)小鼠模式，探討地瓜葉及其萃出物是否增強Cis抗腫瘤效果。裸鼠經皮下注射肺腺癌A549細胞，四周後隨機分成7組，分別為Control (C)、CDDP (2 mg/kg B.W，每週1次)、5% L (單獨飼料中含5%地瓜葉粉末)、CDDP+1或 5% L (飼料中含1或5%地瓜葉粉末)、CDDP+LLE或HLE(地瓜葉萃出物200 或 400 mg/kg B.W，每週灌食3次)，實驗為期12週。結果顯示單獨CDDP給予無法顯著抑制腫瘤生長，合併地瓜葉或其萃出物後，皆可顯著降低腫瘤體積，其中高劑量萃出物效果最佳，另外地瓜葉及萃出物亦降低CDDP所誘發的白血球DNA傷害、血漿中脂質過氧化及血漿或腫瘤組織中促發炎激素TNF-

關鍵字

cisplatin ； A549 ； sweet potato leaves ； quercetin ； cyanidin-3-O-glucoside ； chlorogenic acid ； caffeic acid ； P21 ； P53

並列摘要

Cis-diammine-dichloro-platinum(II)(CDDP；cisplatin) is widely used for treatment of many human cancers. However, the side effects limit the use of CDDP. Quercetin (Q) is a flavonoid with the potential of anti-tumor. In our preliminary study, we determined the content of Q in various vegetables and found that the level of Q in sweet potato leaves was the highest. Therefore, this thesis was divided into two parts to investigate 1.the enhancing effects of sweet potato leaves or it extract on the anticancer effect of CDDP in vivo; and 2. The effects of each phytochemical in the sweet potato leaf extract on the cell-growth-arrest effect of CDDP in A549 cells.

Part 1.
In this study, we used a xenograft model to investigate whether sweet potato leaves or the leaf extract (LE) enhance the antitumor effect of CDDP. Male nude mice were subcutaneously injected with A549 cells. Four weeks after injection, the animals were randomly assigned to the following 7 groups for additional 12 weeks: Control (C), CDDP alone (i.p. 2 mg / kg B.W, once a week), 5% L alone (5% sweet potato leaf powder in diet), CDDP+1% L or 5% L (1and 5% sweet potato leaf powder in diet, respectively) or CDDP+LLE or HLE (200 and 400 mg/kg B.W sweet potato leaf extract 3 times/ week given by gavage, respectively). The results showed that CDDP alone did not significantly inhibit tumor growth. However, CDDP in combination with the high dose of sweet potato leaves or LE significantly reduced tumor volume compared with the control group or CDDP alone group. The antitumor effect of CDDP+HLE was the best. In addition, sweet potato leaves and LE significantly reduced CDDP-induced DNA damage in while cells, the lipid peroxidation in the plasma and inflammatory associated cytokines TNF-α, IL-1β and TGF-β in the plasma or tumor tissues. Sweet potato leaves and LE increased the levels total quercetin and total polyphenol in the plasma or tumor tissues. Taken together, this part of study demonstrate that sweet potato leaves and LE has the potential to enhance the antitumor effect of CDDP accompanied with reducing CDDP-induced oxidative stress and the production of inflammatory associated cytokines.

Part 2.
Our preliminary study showed beside quercetin, sweet potato leaves were also rich in cyanidin-3 -O-glucoside (CY), chlorogenic acid (CH) and caffeic acid (CA). Thus, in this in vitro study, we determined the cell- growth-arrest effects of CDDP (1

並列關鍵字

cisplatin ； A549 ； sweet potato leaves ； quercetin ； cyanidin-3-O-glucoside ； chlorogenic acid ； caffeic acid ； P21 ； P53

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