小蘗鹼抑制肺癌細胞生長之分子作用機轉之研究

小蘗鹼 ( berberine )為異奎啉 ( isoquinoline )類的植物生物鹼，它有很多的藥理作用，包含許多抗發炎以及抗微生物的效果，此外小蘗鹼也可以抑制DNA和蛋白質的合成、阻斷癌細胞的細胞週期進行，以及在裸鼠上可以發現癌細胞的生長抑制。然而，小蘗鹼抗癌細胞的機轉到現在仍然有許多不清楚之處。在本篇論文的實驗中發現，在兩株肺腺癌細胞A549和A549/p53-siRNA中處理小蘗鹼，發現癌細胞明顯被抑制，而且有劑量和時間的依存性。此外，從流式細胞儀分析中也可以發現，兩株細胞皆因為處理小蘗鹼而使細胞週期停滯在G1期。由蛋白質西方點墨法分析的結果顯示，在A549細胞中，處理小蘗鹼造成細胞內cyclin D3、Cdk2和Cdk4蛋白質表現量的降低以及p21的表現量上升。在A549/p53-siRNA也發現同樣現象。同時retionblastoma protein-p130磷酸化現象被抑制。此外，ERK磷酸化以及p38磷酸化分子表現量會提高，可能是小蘗鹼調控這兩株細胞的細胞週期停滯在G1期的關鍵。總結來說，小蘗鹼的確可以藉由調控細胞週期的一些相關分子來抑制肺癌細胞的生長。因此，推測小蘗鹼是一個具有潛力發掘為抗癌藥物的化合物。

關鍵字

小蘗鹼；細胞週期；肺腺癌細胞

並列摘要

Berberine, a plant isoquinoline, isolated from Coptis chinensis, exhibited a remarkable inhibitory effect on protein and DNA synthesis, retarding cancer cell progression through the cell cycle, and inhibition of tumor growth in nude mice. However, the molecular mechanism of berberine-mediated antitumor effect is not fully understand. In this study, we found that treatment of human lung adenocarcinoma A549 and A549/p53-siRNA cells with berberine caused a does- and time-dependent decrease in cell viability. Berberine induced cell cycle G1-phase arrest evidenced by flow cytometric analysis. Treatment with berberine resulted in downregulation of CDK2、CDK4 and CDK1 on both cells. Besides, Berberine-induced cell growth inhibition was accompanied by decreasing the expression levels of cyclin D3 and cyclin E and increasing the expression levels of p21 and pRb2. Taken together, our observations demonstrated that berberine inhibits cancer cell growth by regulating several cell cycle-related molecules. Moreover, berberine induced the phosphorylated activation of ERK and p38. These results suggested that berberine may be a potent anti-cancer drug in the future.

並列關鍵字

berberine ； cycle cycle ； adenocarcinoma

參考文獻

1. Okouoyo S, Herzer K, Ucur E, Mattern J, Krammer PH, Debatin KM, Herr I. Rescue of death receptor and mitochondrial apotosis signaling in resistant human NSCLC in vivo. Int. J. Cancer, 108：580-587 ( 2004 ).

3. Bunn PA Jr, Carney DN. Overview of chemotherapy for small cell lung cancer. Semin Oncol, 24：S7-69-S7-74 ( 1997 ).

6. Huang CG, Chu ZL, Wei SJ, Jiang H,& Jiao BH. Effect of berberine on arachidonic acid metabolism in rabbit platelets and endothelial cells. Thrombosis Res, 106：223–227 ( 2002 ).

7. Wong K K. Mechanism of the Aortic Relaxation induced by low concentrations of berberine. Planta Med, 64：756–757 ( 1998 ).

10. Hong Y, Hui SC, Chan TY, Hou JY. Effect of Berberine on regression of pressure-overload induced cardiac hypertrophy in rats. Am J Chin Med, 30：589–599 ( 2002 ).

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小蘗鹼抑制肺癌細胞生長之分子作用機轉之研究

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