Antibiotic monensin synergizes with EGFR inhibitors and oxaliplatin to suppress the proliferation of human ovarian cancer cells.
Antibiotic monensin synergizes with EGFR inhibitors and oxaliplatin to suppress the proliferation of human ovarian cancer cells.
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抗生素莫能菌素与EGFR抑制剂和奥沙利铂协同抑制人卵巢癌细胞的增殖
DOI：
10.1038/srep17523
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发表时间：
2015-12-07
影响因子：
4.6
通讯作者：
Tang L
中科院分区：
文献类型：
--
作者：
Deng Y;Zhang J;Wang Z;Yan Z;Qiao M;Ye J;Wei Q;Wang J;Wang X;Zhao L;Lu S;Tang S;Mohammed MK;Liu H;Fan J;Zhang F;Zou Y;Liao J;Qi H;Haydon RC;Luu HH;He TC;Tang L
卵巢癌是最致命的妇科恶性肿瘤，总治愈率仅为30%。大多数患者在治愈后12-24个月内复发，并死于进行性化疗耐药疾病。因此，需要更有效的抗卵巢癌疗法。在这里，我们调查的可能性，重新利用抗生素莫能菌素作为抗卵巢癌药物。我们证明莫能菌素有效地抑制细胞增殖，迁移和细胞周期进程，并诱导人卵巢癌细胞凋亡。莫能菌素抑制多种癌症相关通路，包括Elk 1/SRF、AP 1、NFκB和STAT，并降低卵巢癌细胞中EGFR的表达。莫能菌素与EGFR抑制剂和奥沙利铂协同作用，抑制细胞增殖并诱导卵巢癌细胞凋亡。异种移植研究证实，莫能菌素通过靶向EGFR信号传导抑制细胞增殖，从而有效抑制肿瘤生长。我们的研究结果表明，莫能菌素可能被重新用作抗卵巢癌药物，但需要进一步的临床前和临床研究。
Ovarian cancer is the most lethal gynecologic malignancy with an overall cure rate of merely 30%. Most patients experience recurrence within 12–24 months of cure and die of progressively chemotherapy-resistant disease. Thus, more effective anti-ovarian cancer therapies are needed. Here, we investigate the possibility of repurposing antibiotic monensin as an anti-ovarian cancer agent. We demonstrate that monensin effectively inhibits cell proliferation, migration and cell cycle progression, and induces apoptosis of human ovarian cancer cells. Monensin suppresses multiple cancer-related pathways including Elk1/SRF, AP1, NFκB and STAT, and reduces EGFR expression in ovarian cancer cells. Monensin acts synergistically with EGFR inhibitors and oxaliplatin to inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Xenograft studies confirm that monensin effectively inhibits tumor growth by suppressing cell proliferation through targeting EGFR signaling. Our results suggest monensin may be repurposed as an anti-ovarian cancer agent although further preclinical and clinical studies are needed.