桑葉萃取物抑制肥胖促進二乙基亞硝胺致肝癌之作用

Mulberry leaf extract inhibits obesity promoting diethylnitrosamine -induced hepatocellular carcinoma in rats

陳東輝(Dong-Hui Chen)

指導教授 ： 王朝鐘

中山醫學大學/醫學院/醫學研究所/碩士(2016年)

摘要

根據流行病學研究說明，超重和肥胖與癌症風險增加有關。然而，肥胖到底是否會促進肝癌的發生仍屬未知。而桑葉萃取物(MLE)已被證實具有大量的抗氧化和抗發炎能力與改善肥胖之能力，但是MLE是否具有抑制肥胖促進肝癌發生之作用仍未被證實。在本研究中，Sprague Dawley (SD)大鼠以高油脂飼料誘導肥胖，並以含有0.01%的化學致癌物質diethylnitrosamine (DEN)飲用水連續餵食 12週後，誘導大鼠自發性產生肝癌。正如預期，HFD確實增加大鼠的體重與肝臟重量，且大鼠肝臟中的三酸甘油酯(TG)和肝臟中膽固醇的含量也有明顯的上升，相同的趨勢也出現在血液中的三酸甘油酯，總膽固醇和肝臟脂肪變性程度中。重要的是，肥胖確實會增加DEN所誘導肝癌腫瘤的數目，大小以及肝癌發病率。從結果中可以觀察到，MLE可以改善血液中的肝功能指標酵素如ALT，AST，γ-GT與AFP。 MLE還能夠加強大鼠肝臟中的解毒酵素和抗氧化酶的活性。根據上述的結果說明，肥胖確實會增強DEN誘發肝癌的發生，而MLE則具有抑制肝癌發生之能力。這些研究成果未來將有助於肝癌病患達到預防保健的功效。

關鍵字

脂聯素 ； 麩胺基硫轉移酵素 ； 肝細胞癌 ； 高脂飼糧 ； 白細胞介素6 ； c-Jun氨基末端激酶 ； 瘦體素 ； 桑葉萃取物 ； 肥胖 ； 腫瘤壞死因子α

並列摘要

Epidemiological studies indicate that overweight and obesity are associated with increased cancer risk. Mulberry leaf extract (MLE) has been indentified a lot of benefit about anti-oxidant and anti-inflammatory. However, it is unknown whether MLE reduced high fat diet (HFD) induced obesity promotes hepatocarcinogenesis. In this study, Sprague-Dawley rats were induced obesity with HFD (40% beef tallow) and developed hepatomas spontaneously by continuously administering 0.01% diethylnitrosamine (DEN) via drinking water for 12 weeks. As expected, rats maintained on HFD gained more weight than rats on normal diet control group and their relative liver weight was increased as were liver triglycerides (TG) and liver cholesterol. This was accompanied by increased serum TG, total cholesterol and hepatosteatosis. Importantly, when analyzed at rats kept on HFD with DEN exhibited many more HCCs per liver than DEN-only group. Dietary obesity also increased tumor size and incidence. We observed the serum levels of some important enzymes in liver such as ALT, AST, γ-GT and AFP which were decreased by MLE treatment after DEN-induced HCC. MLE also increased detoxification and anti-oxidant enzyme in liver from DEN-induced rat. Our results demonstrate that obesity enhanced DEN-induced HCC development and MLE could inhibit it. These findings will help to further evaluate the potential for the development of new hepatocellular carcinoma therapy.

並列關鍵字

adiponectin ； GST ； HCC ； HFD ； IL-6 ； JNK ； leptin ； MLE ； obesity ； TNF-α

參考文獻

1. Altekruse, S.F., K.A. McGlynn, and M.E. Reichman, Hepatocellular carcinoma incidence, mortality, and survival trends in the United States from 1975 to 2005. J Clin Oncol, 2009. 27: p. 1485-91.

2. Forner, A., et al., Current strategy for staging and treatment: the BCLC update and future prospects. Semin Liver Dis, 2010. 30: p. 61-74.

3. El-Serag, H.B. and K.L. Rudolph, Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 2007. 132: p. 2557-76.

4. Lin, Y.T., H.P. Lu, and C.C. Chao, Oncogenic c-Myc and prothymosin-alpha protect hepatocellular carcinoma cells against sorafenib-induced apoptosis. Biochem Pharmacol, 2015. 93: p. 110-24.

5. Farazi, P.A. and R.A. DePinho, Hepatocellular carcinoma pathogenesis: from genes to environment. Nat Rev Cancer, 2006. 6: p. 674-87.