ABSTRACT
BACKGROUND: Melanoma is known as the most aggressive and lethal type of cutaneous cancer due to its rapid development of drug resistance to chemotherapy drugs. METHODS: In our study, we conducted a variety of studies, including quantitative PCR, Western blot, and autophagy and apoptosis assays to investigate the involvement of miR-26a and HMGB1 in modulation of dabrafenib sensitivity in human melanoma cell lines. RESULTS: Our studies revealed that the expressions of miR-26a and HMGB1 were altered in two melanoma cell lines after dabrafenib treatment. Additionally, dabrafenib caused autophagy in melanoma and this autophagic process was regulated by miR-26a via modifying HMGB1 expression. Furthermore, silencing HMGB1-inhibited autophagy induced by dabrafenib in melanoma cells. Last, we verified that treatment with a miR-26a mimic and HMGB1 shRNA could increase the efficacy of dabrafenib in melanoma cells. CONCLUSION: Taken together, we showed that miR-26a is involved in the regulation of dabrafenib efficacy via a HMGB1-dependent autophagy pathway in melanoma cells. These results shed light on a novel treatment for conventional dabrafenib-based chemotherapy for melanoma.
Subject(s)
Antineoplastic Agents/pharmacology , Autophagy/drug effects , HMGB1 Protein/metabolism , Imidazoles/pharmacology , Melanoma/drug therapy , Melanoma/genetics , MicroRNAs/genetics , Oximes/pharmacology , Cell Proliferation/drug effects , Cell Survival/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Melanoma/metabolism , Melanoma/pathology , Molecular Structure , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
The skin mycoses, perticularly dermatophytoses, in Lanzhou district, Northwestern China, was investigated during July 2002-June 2003. The specimens from patients suspected of having dermatomycoses were examined microscopically in KOH preparations and cultured on Sabouraud dextrose agar (SDA). Among 1443 suspected cases, 594 were KOH positive and 221 cultures of fungi were isolated. The most frequently isolated fungi were Trichophyton rubrum (43.9%) Trichophyton mentagrophytes (29.4%) and Candida species (14.0%). The frequency of tinea pedis, onychomycosis and tinea manuum were 38.7, 27.8 and 13.5%, respectively. In Lanzhou district, tinea pedis is the most commonly seen dermatophytoses, and T. rubrum is the most frequent etiologic agent.
