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  • 學位論文

小蘗鹼抗癌的作用及其可能之機制

The anticancer effects and possible mechanisms of berberine.

指導教授 : 楊繼江

摘要


癌症早已是國內十大死因排名第一位。中草藥中的黃連及其萃取物小蘗鹼先前經本實驗室證實可以抑制口腔中常見菌並具有抗單純皰疹病毒(HSV-1和HSV-2)的作用,先前的文獻也證明小蘗鹼可抑制肺癌、肝癌及口腔癌等細胞,部份文獻也指出小蘗鹼具有抑制癌細胞之細胞週期以及促使細胞凋亡的作用,本研究的目的在探討黃連及小蘗鹼是否對著抗癌細胞生長的功能,結果顯示在細胞方面,藉由MTT assay 可以發現黃連及小蘗鹼對於癌細胞有抑制的作用,PCR arrays 的結果顯示處理小蘗鹼前後許多細胞凋亡相關的基因有明顯的變化,包括: Bcl2、CASP1及TNF等基因。流式細胞儀偵測時可以發現,經由黃連及小蘗鹼處理過的HT-29(人類大腸直腸癌細胞)、T-47D(人類乳腺癌細胞)及BXPC3(人類胰臟癌細胞)細胞所標記上Annexin V螢光的量會明顯的上升,並發現處理過後的細胞會有DNA斷裂的情形,接著藉由測量細胞凋亡蛋白酶caspase-3 可以發現caspase-3含量有上升的趨勢;在動物方面,藥物治療經過異位移植HT-29的裸鼠,其腫瘤生長的速度受到了抑制,本研究可以證實,黃連及小蘗鹼均可有效的抑制HT-29、T-47D、BXPC3等癌細胞的生長。

關鍵字

小蘗鹼 黃連 抗癌 細胞凋亡

並列摘要


In Taiwan, cancers have already become the first of the leading causes of death. As can be seen from previous studies, some Chinese herbal medicine, the Coptidis Rhizoma and berberine, can inhibit the growth of oral common bacteria and herpes simplex virus. Previous literatures have proved that berberine can inhibit the growth of lung cancer cells, liver cancer cells and oral cancer cells. Berberine can induce cell cycle arrest or apoptosis dependent on different cancer cells. In this study, we focus on exploring whether Coptidis Rhizoma and berberine have anti-cancer function in vivo and in vitro. According to the MTT assay, we observed that Coptidis Rhizoma and berberine can inhibit the growth of cancer cells. The results of PCR arrays showed that genes such as BCL2, CASP1, TNF, et al. which are associated with cell apoptosis appear to be affected after the treatment of berberine. As flow cytometry data revealed, the percentages of Annexin V-positive cells, compared with those in negative control, were increased in HT-29, T-47D and BXPC3 cells. Moreover, it is observed that DNA fragmentation and the expression of caspase-3 were increased in the Coptidis Rhizoma or berberine-treated group. The null mice were injected by HT-29 cells in s.c., and it is found the volume of the tumor was inhibited by the treatment in vivo studies. In conclusion, Coptidis Rhizoma and berberine have effectiveness to inhibit the growth of colon, breast and pancreas cancer cells.

並列關鍵字

Cupids Rhizoma Berberine Anticancer Caspase- 3

參考文獻


1. Oxnard, G.R., Miller, V. A., Robson, M. E., et al., Screening for Germline EGFR T790M Mutations Through Lung Cancer Genotyping. J Thorac Oncol, 7(6): p. 1049-52, 2012.
2. Wang, L., McDonnell, S. K., Elkins, D. A., et al., Analysis of the RNASEL gene in familial and sporadic prostate cancer. Am J Hum Genet, 71(1): p. 116-23, 2002.
3. Mignotte, B. and J.L. Vayssiere, Mitochondria and apoptosis. Eur J Biochem, 252(1): p. 1-15, 1998.
5. Giancotti, F.G. and E. Ruoslahti, Integrin signaling. Science, 285(5430): p. 1028-32, 1999.
6. Hannon, G.J. and D. Beach, p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature, 371(6494): p. 257-61,1994.

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