EPIDERMAL GROWTH-FACTOR REGULATES THE INVITRO SENSITIVITY OF HUMAN OVARIAN-CARCINOMA CELLS TO CISPLATIN
EPIDERMAL GROWTH-FACTOR REGULATES THE INVITRO SENSITIVITY OF HUMAN OVARIAN-CARCINOMA CELLS TO CISPLATIN
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DOI：
10.1172/jci114885
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发表时间：
1990-11-01
影响因子：
15.9
通讯作者：
HOWELL, SB
中科院分区：
文献类型：
--
作者：
CHRISTEN, RD;HOM, DK;HOWELL, SB
顺铂(DDP)是目前治疗卵巢癌最有效的药物，但其对DDP细胞毒作用的敏感性机制尚不清楚。同时用表皮生长因子(EGF)处理两种人卵巢癌细胞系，增加了对DDP的敏感性，并在没有任何促分裂作用的情况下引起了持续的形态变化。表达人EGF受体的C127小鼠成纤维细胞，在转铁蛋白受体3‘-诱导调节基因调控下，将含有人EGF受体基因的真核表达载体pBPV导入C127小鼠成纤维细胞后，对DDP的增敏作用依赖于EGF浓度和EGF受体数目。抑制蛋白质合成不能阻断人卵巢癌细胞对DDP的增敏作用。尽管人卵巢癌细胞上存在功能性的EGF受体，但EGF并没有增强这些细胞对DDP的敏感性或改变这些细胞的形态。这些结果表明，EGF激活的信号转导通路元件决定了细胞对DDP的敏感性，并且DDP耐药表型与该信号转导通路的缺陷有关。
Cisplatin (DDP) is the most effective drug for the treatment of human ovarian cancer, but the mechanism that determine sensitivity to the cytotoxic action of DDP are not well understood. Treatment of two human ovarian carcinoma cell lines with epidermal growth factor (EGF) simultaneously increased sensitivity to DDP and caused a prsistent change in morphology in the absence of any mitogenic effect. Sensitization to DDP was shown to be dependent on both EGF concentration and EGF receptor number in C127 mouse fibroblasts expressing the human EGF receptor after transfection with a pBPV plasmid construct containing the human EGF receptor gene under control of the transferrin receptor 3''-inducible regulator. Sensitization of human ovarian carcinoma cells to DDP was not blocked by inhibition of protein synthesis. EGF did not enhance sensitivity to DDP or alter morphology in DDP-resistant human ovarian carcinoma cells despite the presence of functional EGF receptors on these cells. These results showed that elements of the signal transduction pathway activated by EGF determined cellular sensitivity to DDP, and that a DDP-resistant phenotype is associated with a defect in this signal transduction pathway.