Effect Of Valproic Acid On Proliferation Of Human Lung Cancer H1299 And Its Mechanism

Lung cancer has become the most common lethal malignant disease.The vast majority of patients missed the chance of surgical therapy because many of them diagnosed at an advanced stage. Chemotherapy represents a traditional method in the treatment of lung cancer. Nevertheless, acquired resistance to these drugs limits the therapeutic effect of this traditional therapy,especially the patients were treated with the cell cycle specific agents.Identifying new strategies which regulate cell cycle has become critical for developing lung cancer treatments. However, the exact mechanism of cell cycle regulation is not fully understood. Therefore, it is not only important to carry out the research on cell cycle regulation mechanism and intervention strategy, but also has important clinical application value. Valproic acid(VPA) is an acidic organic compound that is an FDA approved anti-seizure and antidepressant drug.In addition to this,VPA is currently being investigated for treating various cancers,but the involved mechanism is largely unknown.In this study, we aimed at cell cycle of lung cancer cells,demonstrating the effect of VPA on inhibiting cancer cell proliferation by inducing cell cycle arrest and apoptosis.our research will explore the potential of VPA as a novel application for lung cancer treatment.In this study, MTT was used to analyze the cellular proliferation,flowcytometry was used to analyzecell cycle and apoptosis, fluorescence quantitative PCR was used to detect mRNA expression, BCA method was used to quantitatively analyze the protein content, and Western blot method was used to analyze the protein expression. The results show that VPA inhibited the proliferation of lung cancer cell A549 and H1299, and VPA arrestedcancer cells at G1/G0 stage,induced the lung cancer cells apoptosis.Ourdata show that these affects are doseand time dependent manner. Our results also show that the p21 expression in VPA treated H1299 cells increased and the CCND1/2expression decreased in VPA treated H1299 cells,whichsuggestedthat VPA could arrestthe lung cancer cell cycle, inhibit the cellular proliferation and introduce cell apoptosis via regulating p21 and CCND1/2 expression.By increase the expression of p21 protein and decrease the expression of CCND1/2 protein, this is the possible way for VPA to cure lung cancer.