Enhanced anti-angiogenic effect of E7820 in combination with erlotinib in epidermal growth factor receptor-tyrosine kinase inhibitor-resistant non-small-cell lung cancer xenograft models.
Bottom Line: Treatment with E7820 (50 mg/kg) with erlotinib (60 mg/kg) showed a synergistic antitumor effect in three xenograft models.Immunohistochemical analysis indicated that combined treatment with E7820 and erlotinib significantly decreased microvessel density and increased apoptosis of tumor-associated endothelial cells compared with use of only one of the agents.This combination increased apoptosis in HUVECs through activation of both intrinsic and extrinsic apoptosis pathways in vitro.
Affiliation: Tsukuba Research Laboratory, Eisai Co., Ltd., Tsukuba, Japan.Show MeSH
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Mentions: We investigated the in vivo antitumor activities of E7820, erlotinib, and E7820 in combination with erlotinib in nude mice bearing erlotinib-resistant NSCLC A549, H1975, or H1650 cells. Approximately 10 days after tumor transplantation, E7820 (25 or 50 mg/kg) and/or erlotinib (60 mg/kg) were given to the mice. The combination of E7820 at either dose with erlotinib showed a superior antitumor effect compared with E7820 or erlotinib alone in three xenograft models (Fig. 1a, Table 1; P < 0.05). The combination of E7820 at a dose of 50 mg/kg with erlotinib at a dose of 60 mg/kg was found to have a significantly synergistic antitumor effect in three xenograft models without severe body weight loss (P < 0.05; Fig. 1b, Table 1). These data show that the combination of E7820 with erlotinib is effective against NSCLC xenograft models resistant to EGFR-TKIs.
Affiliation: Tsukuba Research Laboratory, Eisai Co., Ltd., Tsukuba, Japan.