1 / 2

Terbinafine抑制人類上皮癌細胞﹙A431﹚生長機制之研究

Terbinafine抑制人類上皮癌細胞﹙A431﹚生長機制之研究.

callum-pace
Download Presentation

Terbinafine抑制人類上皮癌細胞﹙A431﹚生長機制之研究

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Terbinafine抑制人類上皮癌細胞﹙A431﹚生長機制之研究Terbinafine抑制人類上皮癌細胞﹙A431﹚生長機制之研究 • Terbinafine (TB) 是一種被廣泛使用的抗黴菌藥物，經過實驗已經證實對人類大腸癌細胞Colo 205可促使其細胞週期停滯於G0/G1期而抑制其生長。 在本實驗中則主要研究TB對人類上皮癌細胞(A431) 的作用機制。首先，在動物實驗中我們發現TB可以明顯的抑制裸鼠的A431腫瘤生長，在組織切片中A431腫瘤以TB治療之後並略為增加了細胞凋亡的現象，而其角質層明顯的增加了。而p21Cip1和p27Kip1在腫瘤上的表現的區域也有明顯的不同，p21Cip1主要表現在分化較差的區域，而p27Kip1則在分化較好的區域表現較多。當以不同濃度的TB處理A431細胞時，隨著 TB濃度的增加，p21Cip1、p27Kip1和Procaspase-3的表現也隨著濃度而增加了，抗細胞凋亡的Bcl-2的表現則是減少了。p21Cip1在附著和自然漂浮的細胞的表現則是和動物實驗中有非常類似的結果，其表現以在附著的細胞有隨TB劑量而增加表現的現象，而在自然漂浮的細胞則是幾乎沒有表現的。不過p27Kip1的表現量在附著和自然漂浮的細胞沒有明顯的差異，但在自然漂浮的細胞有degradation的現象。Bcl-2的表現以在附著的細胞表現較自然漂浮的細胞為多，但在以100 uM TB處理時則恰好相反。Involucrin在自然漂浮的細胞雖然在總表現量上沒有明顯差異，不過其degrade form的表現卻是減少了。在懸浮式培養時p27Kip1的表現同樣也隨著TB的劑量而增加，Bcl-2的表現則幾乎看不到。在以不同劑量的TB處理細胞後，角質細胞分化的Loricrin和 Transglutaminase-1 (TGase-1) 的基因轉錄都增加了，在TB處理後自然漂浮的A431細胞，同樣有增加的趨勢。在此我們發現，TB可能經由增加p21Cip1和p27Kip1及抑制Bcl-2表現的機制，以增加A431細胞分化和細胞凋亡的現象，而抑制了其增生的機制。

  2. Studies on the Mechanism of Terbinafine-induced Anti-Proliferation Effects in Human Epidermal Carcinoma (A431) Cells. • In this study, we demonstrated Terbinafine (TB), the widely used oral- antifungal agents, induces differentiation in human epidermal cancer (A431) cells. TB inhibited the growth of A431 tumor significantly. In TB treated A431 tumor, more p21Cip1 expressed in the less differentiated A431 tumor region, however p27Kip1 was detected more in the well differentiated region. TB increased the expression of p21Cip1 and p27Kip1 expression but decreased the expression of Bcl-2 in A431 cells. TB induced the expression of p21Cip1 in attached A431 cells but not in detached ones. The expression of p27Kip1 was also elevated after the treatment of TB. TB decreased the expression of Bcl-2 which most expressed in the attached A431 cells. In contrast, procaspase-3 expression in attached A431 cells was rised after the TB treatment (25 uM), and the activation of caspase-3 occurred in 100 uM TB treated detached A431 cells. TB also upregulates both mRNA of loricrin and tranglutaminase-1 (TGase-1) which belong to late-stage keratinocyte differentiation markers. After the treatment of TB, the transcription of loricrin and TGase-1 in detached A431 cells were increased, but decreased in attached ones. Our results indicates that TB plays another role in promoting tumor cell differentiation as a potential cancer chemotherapeutic agents.

More Related