Cisplatin and 4-hexylresorcinol synergise to decrease metastasis and increase survival rate in an oral mucosal melanoma xenograft model: a preliminary study
- 208 Downloads
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.
Keywords4-hexylresorcinol Oral mucosal melanoma Cisplatin Matrix metalloproteinases-2
This work was supported by a grant from the Next-Generation BioGreen21 Program (No. PJ009013), Rural Development Administration, Republic of Korea.
- 15.National Toxicology Program. NTP toxicology and carcinogenesis studies of 4-hexylresorcinol (CAS No. 136-77-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies). Toxicol Program Tech Rep Ser. 1988;330:1–166.Google Scholar