探討腫瘤化學治療時藥物作用與細胞凋亡信息傳遞間的關聯性

中山醫學大學機構典藏 CSMUIR > 口腔醫學院 > 牙醫學系暨碩士班 > 研究計劃 > Item 310902500/2887

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题名:	探討腫瘤化學治療時藥物作用與細胞凋亡信息傳遞間的關聯性 The Relationship between the Mechanism of Anticancer Aagents and the Apoptosis Pathway of the Target Cells
作者:	張育超 Chang, Yu-Chao
贡献者:	中山醫學院牙醫學系
关键词:	抗腫瘤;抗腫瘤藥;化學治療;細胞凋亡;訊息傳遞 Antitumor;Antitumor drug;Chemotherapy;Apoptosis;Signal transduction
日期:	2002
上传时间:	2010-11-25T03:43:36Z (UTC)
摘要:	治療腫瘤就是殺傷和清除腫瘤細胞，誘導腫瘤細胞凋亡是治療腫瘤的一條有效途徑，臨床上使用放療及化療的作用機制之一就是引發瘤細胞凋亡。但是正常細胞亦會受到傷害， Matrix metalloproteinases (MMPs) 是一群天然的蛋白水解酵素，其在正常生理狀態下可以分解細胞外基質與基底膜不同的組成，於正常組織重建、血管生成、胚胎發育及病理狀態如癌症侵襲轉移、組織纖維化皆扮演著重要角色。本研究以以組織培養法，培養口腔癌細胞及正常口腔上皮細胞以 zymography 比較其分泌 MMPs 的型態；腫瘤的形成與 protein kinase C (PKC)之訊息傳遞有關，加入 protein kinase C (PKC) inhibitor (H7、 staurosporine) 探討是否由此途徑影響 MMPs 分泌。結果發現口腔癌細胞及正常口腔上皮細胞皆會分泌 MMP-2 及 MMP-9，但口腔癌細胞分泌量較正常口腔上皮細胞高 (P<0.05)。加入無細胞毒性劑量 PKC inhibitor (H7、 staurosporine)可明顯抑制口腔癌細胞分泌 MMP-2 及 MMP-9。 PKC inhibitor 可能成為一種新的抗癌藥物。 The purpose of this study was to investigate gelatinaes (MMP-2 and -9) expression in oral squamous cell carcinoma (SCC) and further explore the potential mechanisms that may lead to inhibit gelatinases activity. Study design. Thirty biopsy specimens of oral SCCs were examined by immunohistochemistry. Supernatants from primary cultures of human oral mucosal keratinocyte (OMK) and oral cancer-derived cells (KB and OC2) were analyzed using gelatin zymography. Furthermore, protein kinase C (PKC) inhibitors (H7 and staurosporine) were added to test how they can modulate the gelatinases production in human oral cancer cells. Results. MMP-2 and ？HV9 expression were significantly higher in oral SCCs and located in discreet clusters of tumor cells. OMK cultures, KB and OC2 were found to secrete and produce MMP-2 and -9. However, the amount of MMP-2 and -9 were highly elevated by two oral cancer cell lines as compared with OMK cultures (P<0.05). In addition, PKC inhibitors were found to decrease MMP-2 and -9 activities in oral cancer cells (P<0.05). Conclusion. Taken together, human oral SCCs produce MMP-2 and -9 in vivo and in vitro and the gelatinases activity are downregulated by PKC inhibitors in vitro. PKC inhibitors suppressing MMPs production and/or activity may therefore be valuable therapeutics in the pathogenesis of oral SCC, and might be proved clinically useful agents, in combination with standard treatment modalities, in the treatment of oral cancer patients.
URI:	https://ir.csmu.edu.tw:8080/handle/310902500/2887
显示于类别:	[牙醫學系暨碩士班] 研究計劃

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