Multidrug resistance (MDR) is the resistance of cells toward various drugs commonly used in tumor treatment. The mechanism of drug resistance in oral cancer is not completely understood. Melatonin is an endogenously produced molecule involved in active biological mechanisms including antiproliferation, oncogene expression modulation, antitumor invasion and migration, and anti-inflammatory, antioxidant, and antiangiogenic effects. Despite these functions, the effects of melatonin on vincristine (VCR)-resistant human oral cancer cells remain largely unknown. This study analyzed the role of melatonin in VCR-resistant human oral cancer cells along with the underlying mechanism. We determined that melatonin induced the apoptosis and autophagy of VCR-resistant oral cancer cells; these actions were mediated by AKT, p38, and c-Jun N-terminal kinase (JNK). Melatonin inhibited ATP-binding cassette B1 (ABCB1) and ABCB4 expression in vitro and in vivo. Melatonin reduced the drug resistance and promoted the apoptosis of VCR-resistant oral cancer cells through the upregulation of microRNA-892a (miR-892a) and miR-34b-5p expressions. The expression of miR-892a and miR-34b-5p was related to melatonin-induced apoptosis, but not autophagy. Therefore, melatonin is a potential novel chemotherapeutic agent for VCR-resistant human oral cancer cell lines.

多药耐药性（MDR）是细胞对肿瘤治疗中常用的多种药物的耐药性。口腔癌的耐药机制尚不完全清楚。褪黑激素是一种内源性产生的分子，参与活性生物机制，包括抗增殖、癌基因表达调节、抗肿瘤侵袭和迁移以及抗炎、抗氧化和抗血管生成作用。尽管有这些功能，褪黑激素对长春新碱（VCR）耐药的人类口腔癌细胞的影响仍然很大程度上未知。本研究分析了褪黑激素在 VCR 耐药人类口腔癌细胞中的作用及其潜在机制。我们确定褪黑激素诱导 VCR 耐药口腔癌细胞的凋亡和自噬；这些作用由 AKT、p38 和 c-Jun N 末端激酶 (JNK) 介导。褪黑激素在体外和体内抑制 ATP 结合盒 B1 (ABCB1) 和 ABCB4 的表达。褪黑素通过上调microRNA-892a（miR-892a）和miR-34b-5p的表达来降低VCR耐药口腔癌细胞的耐药性并促进其凋亡。miR-892a 和 miR-34b-5p 的表达与褪黑激素诱导的细胞凋亡有关，但与自噬无关。因此，褪黑激素是一种潜在的新型化疗药物，用于治疗 VCR 耐药的人类口腔癌细胞系。