title: Cisplatin and 4-hexylresorcinol synergise to decrease metastasis and increase survival rate in an oral mucosal melanoma xenograft model: a preliminary study.
abstract: The present study was undertaken to examine the effects of cisplatin plus 4-hexylresorcinol (4-HR) combination therapy on oral mucosal melanoma (OMM) using cultured primary OMM cells in a tumour xenograft model. Cultured primary OMM cells were used for the MTT assay and DNA microarray. OMM cells were implanted into the submandibular glands of nude mice. The mice were then treated with cisplatin only or cisplatin plus 4-HR. Tumour size changes, survival rate and tumour metastasis were compared between the two groups by observation, micro-positron emission tomography (PET) and histological examination. In the MTT assay, the cisplatin plus 4-HR group showed significantly higher inhibition of OMM cell growth compared to the other groups (p<0.05). DNA microarray results showed significant inhibition of matrix metalloproteinase (MMP)-2 gene expression upon 4-HR application. The necropsy and micro-PET results showed that the mice from the cisplatin-only group had more distant metastases than the mice from the cisplatin plus 4-HR combination group (p=0.002). MMP-2 expression was lower in the primary tumours in the cisplatin plus 4-HR combination group than in the cisplatin-only group (p<0.001). Overall survival was longer in mice from the cisplatin plus 4-HR combination group than in the cisplatin-only group (p=0.049). In conclusion, the combined effect of cisplatin and 4-HR resulted in fewer metastases and longer survival than cisplatin-only treatment in the OMM xenograft model.
authors: Department of Oral and Maxillofacial Surgery, Gangneung-Wonju National University, College of Dentistry, Gangneung, 210-702, Republic of Korea.
authors: Sang-Woon
authors: SW
authors: Lee
authors: Seong-Gon
authors: SG
authors: Kim
authors: Young-Wook
authors: YW
authors: Park
authors: Haeyong
authors: H
authors: Kweon
authors: Jwa-Young
authors: JY
authors: Kim
authors: Horatiu
authors: H
authors: Rotaru
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D004195:Disease Models, Animal; D004357:Drug Synergism; D020869:Gene Expression Profiling; D006604:Hexylresorcinol / Q000494:pharmacology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009061:Mouth Mucosa / Q000187:drug effects / Q000473:pathology; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000871:Anthelmintics; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D002945:Cisplatin; D006604:Hexylresorcinol