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IGF-1R 抑制增强了耐药性卵巢癌细胞早期化疗药物的细胞毒性作用。

IGF-1R inhibition potentiates cytotoxic effects of chemotherapeutic agents in early stages of chemoresistant ovarian cancer cells.

机构信息

Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India.

Gynecologic Oncology, Tata Memorial Hospital, Dr. E Borges Road, Parel, Mumbai, Maharashtra, India.

出版信息

Cancer Lett. 2014 Nov 28;354(2):254-62. doi: 10.1016/j.canlet.2014.08.023. Epub 2014 Aug 23.

Abstract

The kinetics and effect of hyper activated IGF-1R signaling is not well investigated during acquirement of platinum and taxol resistance in ovarian cancer cells. Herein we reported an upregulated IGF-1R expression in early stages of cisplatin paclitaxel and cisplatin-taxol resistance. Picropodophyllin, an IGF-1R inhibitor, alone and in combination with cisplatin, paclitaxel or both at lowest possible doses could reverse the resistance at early stages. Upregulated IGF-1R was also found in primary tumors of ovarian cancer patients after three to four cycles of platinum-taxol treatment. These findings indicate that a combination of cytotoxic agents and IGF-1R inhibitor is more effective at early stages of chemoresistant ovarian cancer.

摘要

在卵巢癌细胞获得铂类和紫杉醇耐药的过程中,高激活 IGF-1R 信号的动力学和作用尚未得到很好的研究。在此,我们报道了 IGF-1R 在顺铂-紫杉醇和顺铂-紫杉醇耐药的早期表达上调。小分子 IGF-1R 抑制剂 picropodophyllin,以最低剂量单独或联合顺铂、紫杉醇或两者均可在早期逆转耐药性。在铂类-紫杉醇治疗三到四个周期后卵巢癌患者的原发肿瘤中也发现了 IGF-1R 的上调。这些发现表明,细胞毒性药物和 IGF-1R 抑制剂的联合使用在化疗耐药性卵巢癌的早期阶段更有效。

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