In vitro and in vivo efficacy of afatinib as a single agent or in combination with gemcitabine for the treatment of nasopharyngeal carcinoma.

ABSTRACT:

Purpose

Epidermal growth factor receptor (EGFR) is usually overexpressed in nasopharyngeal carcinoma (NPC). We tested the antitumor effects of irreversible ErbB family inhibitor afatinib on human NPC using in vitro and in vivo models.

Materials and methods

The effect of afatinib on NPC cells was evaluated using the Cell Counting Kit 8 (CCK8) assay, flow cytometry, and Western blot analyses. The effect of afatinib, as either a single agent or in combination with gemcitabine (GEM), on tumor growth was determined using NPC tumor xenografts in mice.

Results

Afatinib inhibited cell growth in all three NPC cell lines tested in a dose-dependent manner. Afatinib promoted cell cycle arrest at the S and G2/M phases, and it significantly inhibited epidermal growth factor (EGF)-induced activation of EGFR and its downstream signaling factors. Co-treatment with afatinib and GEM more effectively inhibited tumor growth than either drug alone but was associated with increased toxicity.

Conclusion

Afatinib induced cell cycle arrest and inhibited the proliferation of NPC cell lines. Afatinib in combination with GEM demonstrated significant antitumor effect in an NPC xenograft model. The administration of afatinib with GEM in NPC needs to be modified in order to be effective and tolerable.

SUBMITTER: Xue C 

PROVIDER: S-EPMC4821387 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature