ABSTRACT
We report a study on inhibition of human oral squamous cell carcinoma in vitro and in vivo, using novel photosensitizer (PS) aloe emodin (AE) mediated photodynamic therapy (PDT). Distinct morphology changes of oral mucosa carcinoma KB cells were observed under an optical microscope and cell migrations were inhibited owing to AE-PDT. The cell proliferation was blocked in G1 phase and the apoptosis increase were both caused by massive reactive oxygen species (ROS) generated from photoactivated AE. The upregulation of Caspase-3 and Bax protein levels and downregulation of Bcl-2 protein levels were observed after AE-PDT. The survival time of tumor mouse was prolonged without side effects ascribed to AE-PDT and its inhibitory effect on mice transplantation tumors was significant. It is indicated that AE mediated PDT is an innovative way to oral cancer treatment with the dominances of effectivity, minimal invasion, tissue integrity retention and none side effects on main organs.
Subject(s)
Anthraquinones/administration & dosage , Carcinoma, Squamous Cell/drug therapy , Mouth Neoplasms/drug therapy , Photochemotherapy/methods , Animals , Anthraquinones/adverse effects , Anthraquinones/pharmacology , Apoptosis/drug effects , Carcinoma, Squamous Cell/pathology , Cell Movement/drug effects , Cell Proliferation/drug effects , Gene Expression Regulation, Neoplastic , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Mouth Mucosa/pathology , Mouth Neoplasms/pathology , Neoplasm Transplantation , Photochemotherapy/adverse effects , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/adverse effects , Photosensitizing Agents/pharmacology , Reactive Oxygen Species/metabolism , Survival RateABSTRACT
OBJECTIVES: The aim of this study was to determine expression levels of miR-433 in oral squamous cell carcinomas (OSCCs) and adjacent normal tissues, and explore its biological functions in OSCCs. METHODS: miR-433 level in oral squamous cell carcinomas (OSCCs) and adjacent normal tissues was tested by real-time qPCR. The effect of miR-433 on cell growth was detected by MTT and colony formation assays. The tumorigenicity of miR-433 transfected OSCCs was evaluated in nude mice model. Transwell and wound healing assays were performed to detect the effect of miR-433 on OSCCs cell invasion and migration. Luciferase reporter gene assays were performed to identify the interaction between miR-433 and 3'UTR of HDAC6 mRNA. The protein level of HDAC6, BCL2, CCNE1, MMP1 and MMP9 was determined by Western blotting. Immunohistochemistry analysis was performed to detect the expression of HDAC6 in oral squamous cell carcinomas (OSCCs) and adjacent normal tissues. RESULTS: We found that miR-433 was frequently down-regulated in OSCCs compared with adjacent normal tissues. Restoring miR-433 expression in OSCC cells dramatically suppressed cells growth, invasion and migration. Importantly, our data showed that miR-433 downregulated the expression of HDAC6 through directly targeting its 3'UTR. CONCLUSION: Our data suggest that miR-433 exerts its tumor suppressor function by targeting HDAC6, leading to the inhibition of OSCC cell growth, invasion and migration, which suggest that miR-433 may be potential target for diagnostic and therapeutic applications in OSCC.
