OP221: In vitro and in vivo inhibition effects of artesunate on a novel human palatal salivary gland adenoid cystic carcinoma cell line

Abstract

To investigate the effects of artesunate on adenoid cystic carcinoma cell line named NACC. Cell growth inhibition was detected by methyl thiazolyl tetrazolium and clone formation assaies after NACC cell line were treated with various concentrations of artesunate in vitroly, morphological changes were observed by inverted microscopy and electron microscopy. Wound healing and flow cytometry assay was used to analyze NACC cell migration, cell cycles and cell apoptosis after artesunate treated. NACC cells were inoculated subcutaneous into BABL-C nude mice for xenografts and treatment started on the 7th day when solid tumors were palpated, grouping as: control, artesunates, cialpatin and artesunate plus cialpatin treated groups. Drugs were given everyother days for eight times. On the 23th day, the animals were sacrificed then tumors were excised and weighted. Tumors were also investigated by immunohistochemistry and western bloting. The 25–200 μg/ml artesunate produced proliferation inhibition and apoptosis induction on NACC cell line in a time-and does-dependent manner. IC 50 of artesunate in 24, 48 and 72 h were 113.09, 74.80, 35.61 μg/ml respectively. Cell cycle of NACC cell could be arrested the in G1 phase by 12.5–50.0 μg/ml and G2 phase by 50.0–200.0 μg/ml of artesunate. Artesunate could change the morphological structure and significantly inhibited the migration and clone formation of NACC cell. Artesunate 200 mg/kg groups efficiently inhibited the growth of NACC xenograft; artesunate 50 mg/kg combined with cisplatin 1.0 mg/kg also resulted in significant growth inhibit of the tumors. VEGF, Bcl-2, ERK2 were down-regulated in ART 100 mg/kg, ART 200 mg/kg and ART plus DDP groups. In artesunate 200 mg/kg and ART plus DDP groups had different degrees of down-regulation of CXCR4, CD44, CD133 express. ART might significantly inhibit the growth of NACC cell in vitro and in vivo, by adjusting the cell cycle, inducing apoptosis and inhibiting neovascularization.