A potential synergistic anticancer effect of paclitaxel and amifostine on endometrial cancer
A potential synergistic anticancer effect of paclitaxel and amifostine on endometrial cancer
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DOI：
10.1158/0008-5472.can-05-1613
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发表时间：
2005-10-15
期刊：
影响因子：
11.2
通讯作者：
Leslie, KK
中科院分区：
文献类型：
--
作者：
Dai, DH;Holmes, AM;Leslie, KK
虽然紫杉醇是最有效的化疗药物之一，但其在晚期和复发性子宫内膜癌中的作用仍然有限。氨磷汀保护正常组织免受化疗药物的副作用已在癌症患者中得到临床证明;然而，其在子宫内膜癌中的应用尚未得到充分评价。我们研究了紫杉醇和氨磷汀在体外和体内控制低分化子宫内膜癌细胞Hec 50 co生长的作用。我们的研究表明氨磷汀在体外对子宫内膜癌细胞具有直接的抗肿瘤作用，其作用机制是通过将细胞周期阻滞在G（1）期并诱导细胞凋亡。氨磷汀也能抑制s.c.无胸腺小鼠的肿瘤生长。氨磷汀178 μ mol/L预处理72小时后，紫杉醇的IC_（50）值由14 nmol/L降至2 nmol/L。氨磷汀还与紫杉醇在将细胞周期阻滞在G（2）-M期和诱导凋亡方面具有协同作用。这两种药物方案抑制s.c.肿瘤生长以及改善小鼠存活率的作用显著高于单独的紫杉醇。氨磷汀还显著改善紫杉醇诱导的外周血细胞毒性作用。我们的研究表明氨磷汀对子宫内膜癌有直接的抗癌作用。我们的数据还显示了氨磷汀和紫杉醇在体外和体内的潜在抗癌协同作用，而氨磷汀在外周血中保持了保护作用。氨磷汀作用的双重特异性应进一步研究。
Although paclitaxel is one of the most effective chemotherapeutic agents, its usefulness is still limited in advanced and recurrent endometrial cancer. Amifostine protection of normal tissues against the side effects of chemotherapeutic agents has been clinically proven in cancer patients; however, its application in endometrial cancer has not been fully evaluated. We have investigated the use of paclitaxel and amifostine in controlling the growth of poorly differentiated endometrial cancer cells, Hec50co, in vitro and in vivo. Our studies show that amifostine had direct anticancer effects on endometrial cancer cells in vitro by arresting the cell cycle at the G(1) phase and inducing apoptosis. Amifostine also inhibited s.c. tumor growth in athymic mice. Paclitaxel IC50 value was reduced from 14 to 2 nmol/L with pretreatment of a single dose of 178 mu mol/L of amifostine for 72 hours. Amifostine also synergized with paclitaxel in the arrest of the cell cycle at the G(2)-M phase and in the induction of apoptosis. This two-drug regimen inhibited s.c. tumor growth as well as improved mouse survival significantly more than paclitaxel alone. Amifostine also significantly improved paclitaxel-induced cytotoxic effects on peripheral blood profiles. Our studies show that amifostine has direct anticancer effects on endometrial cancer. Our data have also shown a potential anticancer synergy between amifostine and paclitaxel in vitro and in vivo, whereas amifostine maintained a protective role in peripheral blood profiles. The dual specificity of amifostine action should be further investigated.