Therapeutic targeting of the endothelin a receptor in human nasopharyngeal carcinoma
Therapeutic targeting of the endothelin a receptor in human nasopharyngeal carcinoma
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DOI：
10.1111/j.1349-7006.2006.00333.x
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发表时间：
2006-12-01
期刊：
影响因子：
5.7
通讯作者：
Hong, Ming-Huang
中科院分区：
文献类型：
--
作者：
Mai, Hai-Qiang;Zeng, Zong-Yuan;Hong, Ming-Huang
The endothelin A receptor (ETAR) autocrine pathway is overexpressed in many malignancies, including nasopharyngeal carcinoma (NPC). In this tumor, ETAR expression is an independent determinant of survival and a robust independent predictor of distant metastasis. To evaluate whether ETAR represents a new target in NPC treatment, we tested the therapeutic role of ETAR in NPC. Cell proliferation was inhibited by the ETAR-selective antagonist ABT-627 in two ETAR-positive NPC cells in a dose-dependent manner. Proliferation of ETAR-negative NPC cells was not decreased. ETAR blockade also resulted in sensitization to cisplatin and 5-fluorouracil-induced apoptosis. In nude mice, ABT-627 inhibited the growth of NPC cell xenografts. Combined treatment of ABT-627 with the cytotoxic drug cisplatin or 5-fluorouracil produced additive antitumor effects. The antitumor activity of ABT-627 was demonstrated finally on an experimental lung metastasis by a reduction in the number of tumors. These results support the rationale of combining ABT-627 with current standard chemotherapy to further improve the therapeutic ratio in the treatment of NPC.
