散腫潰堅湯 (San-Zhong-Kui-Jian-Tang , SZKJT)，是一個傳統的中藥方劑，已用在治療各種癌症的病人。據古書記載，其具有清熱解毒、破結潰堅之效能；亦即今日臨床之抗菌、抗腫瘤、鎮痛的作用；因此本研究首要在探討將散腫潰堅湯用在兩個乳癌細胞株 MCF-7及 MDA-MB-231 的抗癌效果。散腫潰堅湯藉由誘導癌細胞走向 G0/G1 phase arrest 及細胞凋亡 (Apoptosis)，而呈現出抑制細胞生長的作用。散腫潰堅湯可透過增加 p21/WAF1 表現，降低 cyclin D1、D2 的蛋白質量，而達到抑制細胞週期演進的效果；然而，由於散腫潰堅湯並不會增加 MCF-7 之 p53 的表現，因此都不是藉由 p53 的作用而來。使用散腫潰堅湯處理的癌細胞，會藉由改變 Bax/Bcl-2 的比例，而啟動粒線體細胞凋亡的路徑，使得 cytochrome c 釋放以及 caspase-9 活化；但並未作用在 Fas/Fas ligand 路徑及 caspase-8 的活化。在裸鼠實驗中更進一步的證明了散腫潰堅湯對癌細胞生長的抑制作用。因此我們的研究推測出對 p21/WAF1 的誘導作用以及活化粒線體細胞凋亡系統參與了散腫潰堅湯在人類乳癌細胞的抗增生活性。 San-Zhong-Kui-Jian-Tang (SZKJT; Japanese name: Sanshu-kaigen-to), a traditional Chinese medicine prescription, has been used for treating patients with various cancers. This study first investigates the anticancer effect of SZKJT in two human breast cancer cell lines, MCF-7 and MDA-MB-231. SZKJT exhibited effective cell growth inhibition by inducing cancer cells to undergo G0/G1 phase arrest and apoptosis. Blockade of cell cycle was associated with increased p21/WAF1 levels, and reduced amounts of cyclinD1, cyclinD2 in a p53-independent manner. SZKJT treatment triggered the mitochondrial apoptotic pathway indicated by changing Bax/Bcl-2 ratios, cytochrome c release and caspase-9 activation, but did not act on Fas/Fas ligand pathways and the activation of caspase-8. Further investigation revealed that SZKJT’s inhibition of cell growth effect was also evident in a nude mice model. Taken together, our study suggests that the induction of p21/WAF1 and activity of the mitochondrial apoptotic system may participate in the antiproliferative activity of SZKJY in human breast cancer cells.
