Chemical Oral Cancerogenesis Is Impaired in PI3Kγ Knockout and Kinase-Dead Mice

We investigated the role of PI3Kγ in oral carcinogenesis by using a murine model squamous carcinoma generated exposure to 4-nitroquinoline 1-oxide (4NQO) and continuous human cancer cell line HSC-2 Cal-27. knockout (not expressing PI3Kγ), kinase-dead (carrying mutation gene causing loss kinase activity) wild-type (WT) C57Bl/6 mice were administered 4NQO via drinking water induce carcinomas. At sacrifice, lesions histologically examined stained for prognostic tumoral markers (EGFR, Neu, cKit, Ki67) inflammatory infiltrate (CD3, CD4, CD8, CD19 CD68). Prevalence incidence preneoplastic exophytic significantly similarly delayed both transgenic versus control. The expression markers, as well CD19+ CD68+ cells, was higher WT, while T lymphocytes more abundant tongues isolated from mice. Cal-27 cells cultured presence specific PI3Kγ-inhibitor (IPI-549) which impaired vitality dose-dependent manner, shown MTT test. Here, we highlighted two different mechanisms, namely modulation tumor-infiltrating direct inhibition cancer-cell proliferation, might impair cancerogenesis absence/inhibition PI3Kγ.