Suppression of ovarian cancer cell tumorigenicity and evasion of Cisplatin resistance using a truncated epidermal growth factor receptor in a rat model.

摘要: The overexpression of the epidermal growth factor receptor (EGFR) is associated with a poor prognosis in ovarian cancer. dominant-negative EGFR (EGFR-DNR) truncated that lacks tyrosine kinase domain and devoid signaling capability. This study tested effects EGFR-DNR approach cancer cells. NuTu-19, rat cell line was rendered resistant to cisplatin. Both NuTu-19 cells were infected retroviral vector containing EGFR-DNR. NuTu-DNR (NuTu-19 expressing EGFR-DNR) injected into Fisher 344 immunocompetent rats. Western blot analyses used assess signal transduction pathways. All rats remained healthy following tumor injection. In contrast, 100% NuTu-Sham an empty vector) died disease progression at end 15 weeks (P = 0.00009). On analysis, both showed strong activation mitogen-activated protein (MAPK) after exposure EGF. Cisplatin-resistant lines enhanced EGF stimulatory effect via MAPK pathway compared parental significantly reduced ability induce through pathway. Lastly, can partially reverse cisplatin resistance drug-resistant suggests confers advantage vivo. Thus, blockade may ultimately prove be useful therapeutic tool treatment cisplatin-sensitive cisplatin-resistant cancers.