https://scholars.lib.ntu.edu.tw/handle/123456789/193530
標題: | Epidermal Growth Factor Receptor Inhibitor (Pd168393) Potentiates Cytotoxic Effects of Paclitaxel against Androgen-Independent Prostate Cancer Cells 上皮生長因子 (Pd168393) 可加強太平洋紫杉醇對荷爾蒙抗性前列 腺癌之化學治療效果 |
作者: | PU, YEONG-SHIAU HSIEH, MIN-WEI WANG, CHUANG-WEI LIU, GUANG-YAW HUANG, CHAO-YUAN LIN, CHIA-CHI GUAN, JING-YI LIN, SHINNE- REN HOUR, TZYH-CHYUAN 蒲永孝 謝旻娓 王壯維 劉光耀 黃昭淵 林家齊 官靜儀 林信仁 侯自銓 |
關鍵字: | TYROSINE KINASE INHIBITOR;CARCINOMA-CELLS;ZD1839 IRESSA;LUNG -CANCER;IN-VITRO | 公開日期: | 2006 | 卷: | v.71 | 期: | n.6 | 起(迄)頁: | 751-760 | 來源出版物: | BIOCHEMICAL PHARMACOLOGY | 摘要: | Recent data showed that epidermal growth factor receptor ( EGFR) inhibitors, such as ZD1839, alone or in combination with chemotherapeutic agents for androgen-independent prostate cancer (AIPC) did not produce promising results in clinical settings. More effective regimens involving novel stronger inhibitor of EGFR and better combinations are needed. The anti-tumor activity of PD168393, an irreversible EGFR inhibitor, with or without chemotherapeutic agents for the treatment of AIPC was investigated in vitro. in results , both the androgen-independent cell lines PC-3 and DU145 expressed higher levels of EGFR than the androgen-dependent MDA PCa 2b and androgen-responsive LNCaP cells by Western blotting. DU145 was much more sensitive to PD168393 and ZD 1839 than MDA PCa 2b. PD168393, but not ZD1839, significantly potentiated paclitaxel cytotoxicity against DU 145 by MTT assay and median-effect analysis. The combination of PD168393 or ZD 1839 with other cytotoxic agents including docetaxel and 5-fluorouracil, however, was either additive or antagonistic. Compared to paclitaxel alone , PD168393 significantly enhanced paclitaxel-induced DNA fragmentation, sub-G1 fraction accumulation, mitochondrial membrane dysfunction, cytochrome C release, caspase-3 activation and eventually apoptosis. These molecular events were accompanied by Bad up-regulation, p53 and p21(Waf1/ Cip1) induction, ERK1/2 inactivation and inhibition of EGFR phosphorylation in the presence of PD 168393. These effects did not involve significant alteration in the Akt1/2 and STAT3 signaling pathway. In conclusion, the combination of paclitaxel and PD168393 produced a profound synergistic growth inhibition of AIPC cells. Combining PD168393 with paclitaxel may have clinical benefits and warrants further investigation. |
URI: | http://ntur.lib.ntu.edu.tw//handle/246246/94243 |
顯示於: | 醫學系 |
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