PRIMA-1MET synergizes with cisplatin to induce tumor cell apoptosis
PRIMA-1MET synergizes with cisplatin to induce tumor cell apoptosis
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DOI：
10.1038/sj.onc.1208419
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发表时间：
2005-05-12
期刊：
影响因子：
8
通讯作者：
Wiman, KG
中科院分区：
文献类型：
--
作者：
Bykov, VJN;Zache, N;Wiman, KG
携带突变型p53的肿瘤通常对化疗药物更具抗性。我们在这里证明，突变型p53再活化化合物PRIMA-1（MET）与几种化疗药物协同作用，抑制肿瘤细胞生长。顺铂和PRIMA-1（MET）的联合治疗可协同诱导SCID小鼠体内肿瘤细胞凋亡并抑制人肿瘤异种移植物生长。化疗药物诱导突变型p53水平可能会增加肿瘤细胞对PRIMA-1（MET）的敏感性。因此，PRIMA-1（MET）与目前使用的化疗药物的组合可能代表了一种新的和更有效的治疗策略，用于治疗携带突变型p53的肿瘤。
Mutant p53-carrying tumors are often more resistant to chemotherapeutical drugs. We demonstrate here that the mutant p53-reactivating compound PRIMA-1(MET) acts synergistically with several chemotherapeutic drugs to inhibit tumor cell growth. Combined treatment with cisplatin and PRIMA-1(MET) resulted in a synergistic induction of tumor cell apoptosis and inhibition of human tumor xenograft growth in vivo in SCID mice. The induction of mutant p53 levels by chemotherapeutic drugs is likely to increase the sensitivity of tumor cells to PRIMA-1(MET). Thus, the combination of PRIMA-1(MET) with currently used chemotherapeutic drugs may represent a novel and more efficient therapeutic strategy for treatment of mutant p53-carrying tumors.