INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase, enhances tumor response to doxorubicin
INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase, enhances tumor response to doxorubicin
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DOI：
10.1007/s10637-007-9072-5
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发表时间：
2008-02-01
影响因子：
3.4
通讯作者：
Milas, Luka
中科院分区：
文献类型：
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作者：
Mason, Kathryn A.;Valdecanas, David;Milas, Luka
聚（ADP-核糖）合成酶抑制剂 INO-1001 已知可通过抑制 DNA 损伤的修复来使细胞对体外辐射敏感。最近的证据表明，PARP 抑制也可能是选择性靶向 p53 缺陷癌细胞的一种方法。本研究测试了 INO-1001 对两种 p53 缺陷肿瘤（人乳腺癌 MDA-MB-231 和鼠乳腺癌 MCa-K）化疗反应的体内作用。阿霉素用作 DNA 损伤剂，肿瘤生长延迟测定用作终点。结果表明，INO-1001 能够高效增强阿霉素对 MDA-MB-231 (EF=1.88) 和 MCa-K (EF=1.64) 的抗肿瘤作用。我们得出的结论是，PARP 抑制剂 INO-1001 具有增强化疗药物（如阿霉素）针对 p53 缺陷型乳腺癌的抗肿瘤作用的巨大潜力。
Poly(ADP-ribose) synthetase inhibitor, INO-1001, is known to sensitize cells to radiation in vitro by inhibiting the repair of DNA damage. Recent evidence has suggested that PARP inhibition may also be a way of selectively targeting p53 deficient cancer cells. The present study tested INO-1001 for its in vivo effect on the chemoresponse of two p53 deficient tumors, human breast cancer MDA-MB-231 and murine mammary carcinoma MCa-K. Doxorubicin was used as the DNA damaging agent and tumor growth delay assay was used as the endpoint. Results showed that INO-1001 was highly effective in enhancing the anti-tumor effects of Doxorubicin for both MDA-MB-231 (EF=1.88) and MCa-K (EF=1.64). We conclude that PARP inhibitor INO-1001 has high potential for enhancing the anti-tumor effects of chemotherapy agents such as Doxorubicin against p53 deficient breast cancer.