The Effect Of Valproic Acid On Biological Behavior Of Oral Squamous Cell Carcinoma Cell Line Cal-27

Objective:Oral squamous cell carcinoma is a common malignant tumor in oral and maxillofacial region. Generally, it is treated by sequence therapy consisting of surgery, radiotherapy, chemotherapy, biological therapy. However, in the recent20years, the five-year survival rate of patients with oral malignancy has been remaining at50%, which is even lower with advanced tumor. In order to regulate gene expression, Histone deacetylase (HDAC) and Histone acetyltransferases (HAT) dynamically adjust the affinity of histone and DNA moderate chromatin. Previously, researchers found that many tumors developed with an abnormal regulation of HDAC. Valproic acid, a classic anti-epileptic drug, may become a new type of anticancer drugs because recent study found that it could inhibit HDAC and consequently affected the biological behavior of the tumor, such as proliferation, apoptosis, cell cycle and differentiation. This study aimed to investigate how valproic acid affected oral squamous cell carcinoma cell lines CAL-27as well as the potential mechanism for oral tumor treatment.Methods:1. To observe cell morphology change of CAL-27induced by valprioc acid via inverted phase contrast microscope.2. To detect the toxicity and inhibitory effects of valproic acid on the growth of CAL-27cells via methylthiazolyltetrazolium assay (MTT assay)3. To detect the apoptosis and cell cycle of CAL-27induced by valproic acid via flow-cytometry.4. To detect the mRNA change of SUMO related genes during CAL-27differentiation and apoptosis induced by valproic acid via real time fluorescence quantitative PCR. Results:1. With valproic acid concentration increased, inhibitory effect on growth of CAL-27gradually strengthened as well as the apoptosis rate, but at a concentration of2mM perform significantly. CAL-27cells were treated with valproic acid for24hours, when cell cycle arrest with G1phase increased, S phase decreased, and the G2phase changed unobviously, statistically significant difference.2. An indicator of CAL-27cell differentiation, involucrin, mRNA level increased significantly when cells were treated with valproic acid at2mM up to24hours.3. During the process of CAL-27cell differentiation and apoptosis, SENP1mRNA level downregulated at12hours, while SENP3, SUM01and SUM02increased.Conclusions:1. Valproic acid could inhibit the growth of oral squamous cell carcinoma cell line CAL-27cells. During the process, cell cycle arrested, cell apoptosis increased and cell began to differentiate.2. Some of small ubiquitin-like modifier (SUMO) gene profile changed during CAL-27cell apoptosis and differentiation induced by valproic acid, the SUMO pathway possibly participate the process.