| Abstract: | 非固醇類抗炎性藥物(NSAIDs)如阿斯匹靈(aspirin, acetylsalicylic acid,ASA)已知為許多腫瘤之化學治療藥物。然而其所牽涉 之訊息傳導物質則仍未明確。本實驗目的乃在探討ASA所誘發細胞凋亡之可能路徑p53路徑。以不同濃度之ASA(0, 0.5, 1, 2, and 4 mM)處理，可使細胞外形顯著改變、降低細胞存活率及DNA片段鏈解，顯示ASA能誘發細胞凋亡。同時，不論是在時間或劑量的實驗中p53蛋白質表現皆伴隨ASA劑量之增加而增 加。Cox-2則降低。Caspase-3於ASA處理後3小時既顯著誘發。當以ERK抑制劑PD98059抑制ERK活性時p53蛋白質顯著增加，此顯示 ERK 扮 演相對之角色。ASA藉由p53路徑誘發細胞之凋亡且與ERK之活性表現有關。
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic acid (ASA, also called aspirin) are well known chemotherapeutic agents of cancers; however, the signaling molecules involved remain unclear. The aim of this study was to investigate the possible existence of a putative p53-dependent pathway underlying the acetylsalicylic acid-induced apoptosis in OC-2 cells, a human oral cancer cell line. By increasing concentrations of ASA (0, 0.5, 1, 2, and 4 mM), changes in morphology leading to cell death took place. The MTT assay was employed to quantify differences in cell activity and viability. DNA ladder formation on agarose electrophoresis was also performed. The expression levels of several master regulatory molecules controlling various signal pathways were monitored using the immunoblotting techniques. Patterns of changes in expression were scanned and analyzed using the NIH image 1.56 software. Drastic morphological changes, reduced cell viability, and presence of internucleosomal DNA fragmentation all indicated that ASA is capable of inducing apoptosis in OC-2 cells. In the meanwhile, accumulation of wild type p53 protein significantly increased in time- and dose-dependent manners upon treatment with ASA. The expression of Cox-2 significantly decreased in response to ASA. The caspase-3 induced early at 3 hours after treated with ASA. The p53 protein induction by ASA was markedly enchanced when ERK activation was inhibited by ERK-specific inhibitor PD098059, thus indicating a negative role for ERK. ASA can induce apoptosis via p53-dependent pathway, at least, in cells from this particular oral cancer cell line. Furthermore, the expression of p53 was involved of ERK 1/2 blocking in response to treatment with ASA. |
