Elemene displays anti-cancer ability on laryngeal cancer cells in vitro and in vivo
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Purpose: The goal of this study is to investigate the inhibitory effects and mechanism of elemene on the growth of laryngeal cancer cells in vitro and in vivo. Methods: Laryngeal cancer cells (HEp-2 cells) were grown in elemene, cisplatin, or a combination of the drugs. The cytotoxic, or apoptotic, effects of elemene on the cells were evaluated by a 3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide assay, flow cytometry, and a caspase-3 activity assay. A Western blot was used to semi-quantify the protein expression of eukaryotic initiation factors (eIF4E and eIF4G), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF); RT-PCR analysis semi-quantified the mRNA transcript expression of bFGF and VEGF. The HEp-2 cells were transplanted subcutaneously to BALB/c nude mice to produce solid tumors. Elemene and cisplatin were administered to the mice either as individual drugs or in combination. The tumors were excised and immunostained to determine the effect each drug had on tumor size, eIF levels, angiogenic factors, and microvessel density (MVD). Results: Elemene inhibited the growth of HEp-2 cells in vitro in a dose- and time-dependent manner with an IC50 of 346.5 μM (24 h incubation). Increased apoptosis was observed in elemene-administered cells. Elemene is suspected to enhance caspase-3 activity, and thus inhibit protein expression of eIFs (4E, 4G), bFGF, and VEGF. In vivo, the growth of HEp-2 cell-transplanted tumors in nude mice was inhibited by intraperitoneal injection of elemene. Compared with control groups, elemene significantly inhibited the protein expression of eIFs (4E and 4G), bFGF, and VEGF and decreased the MVD. Conclusions: Elemene inhibits the growth of HEp-2 cells in vitro and in vivo. These data provide useful information for further clinical study on the treatment of LSCC by elemene.
KeywordsElemene Laryngeal squamous cell carcinoma Apoptosis EIF Angiogenesis
Basic fibroblast growth factor
Eukaryotic initiation factor
Laryngeal squamous cell carcinoma
Vascular endothelial growth factor
We thank the staff of the Department of Experimental Rheumatology, Shanghai Renji Hospital, for their technical support and expertise. We are also grateful to Pr. Jack Jiang from the division of otolaryngology-HNS, University of Wisconsin Medical School, and Pr. Jean-François Bernaudin from the department of histology and tumor biology, Tenon Hospital, University of Paris VI for their valuable advice.
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