Li Yiwei, Hussain Maha, Sarkar Sarah H, Eliason James, Li Ran, Sarkar Fazlul H
Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.
BMC Cancer. 2005 Jan 18;5:7. doi: 10.1186/1471-2407-5-7.
Both Taxotere and Capecitabine have shown anti-cancer activity against various cancers including prostate cancer. In combination, Taxotere plus Capecitabine has demonstrated higher anti-cancer activity in advanced breast cancers. However, the molecular mechanisms of action of Taxotere and Capecitabine have not been fully elucidated in prostate cancer.
The total RNA from PC3 and LNCaP prostate cells untreated and treated with 2 nM Taxotere, 110 microM Furtulon (active metabolite of Capecitabine), or 1 nM Taxotere plus 50 microM Furtulon for 6, 36, and 72 hours, was subjected to Affymetrix Human Genome U133A Array analysis. Real-time PCR and Western Blot analysis were conducted to confirm microarray data.
Taxotere and Furtulon down-regulated some genes critical for cell proliferation, cell cycle progression, transcription factor, cell signaling, and oncogenesis, and up-regulated some genes related to the induction of apoptosis, cell cycle arrest, and differentiation in both cell lines. Taxotere and Furtulon also up-regulated some genes responsible for chemotherapeutic resistance, suggesting the induction of cancer cell resistance to these agents.
Taxotere and Furtulon caused the alternation of a large number of genes, many of which may contribute to the molecular mechanisms by which Taxotere and Furtulon inhibit the growth of prostate cancer cells. This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against prostate cancer.
多西他赛和卡培他滨已显示出对包括前列腺癌在内的多种癌症具有抗癌活性。联合使用时，多西他赛加卡培他滨在晚期乳腺癌中已证明具有更高的抗癌活性。然而，多西他赛和卡培他滨在前列腺癌中的分子作用机制尚未完全阐明。
对未处理以及用2 nM多西他赛、110 microM氟铁龙（卡培他滨的活性代谢物）或1 nM多西他赛加50 microM氟铁龙处理6、36和72小时的PC3和LNCaP前列腺细胞的总RNA进行Affymetrix人类基因组U133A阵列分析。进行实时PCR和蛋白质印迹分析以确认微阵列数据。
多西他赛和氟铁龙下调了一些对细胞增殖、细胞周期进程、转录因子、细胞信号传导和肿瘤发生至关重要的基因，并上调了一些与诱导凋亡、细胞周期停滞和两种细胞系分化相关的基因。多西他赛和氟铁龙还上调了一些负责化疗耐药性的基因，表明诱导癌细胞对这些药物产生耐药性。
多西他赛和氟铁龙导致大量基因发生改变，其中许多基因可能有助于多西他赛和氟铁龙抑制前列腺癌细胞生长的分子机制。这些信息可用于进一步的机制研究以及设计针对前列腺癌的优化治疗策略。
Zotero 插件
