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