ABSTRACT
Background and purpose: Trichostatin A (TSA), an antifungal antibiotic with cytostatic and differentiating properties in mammalian cell culture, is a potent and specific inhibitor of histone deacetylase (HDAC). This study was aimed to investigate the influence of trichostatin A on the growth of human lung adenocacinoma cells in vitro, and to explore the mechanisms involved. Methods: MTT assay was employed to evaluate the inhibitory effect of TSA (0.1, 0.2,0.4 μmol/L) on the growth of human NCI-H1299 cancer cells. The cell cycle distribution and apoptotic ratio were determined by flow cytometry. The acetyl level of histone H4 after TSA treatment was detected by Western blot;the mRNA level of Bax,Bcl-2,p21 and cyelinBl was measured by Real-time PCR. Results: TSA inhibited the growth of NCI-H1299 cells in a dose-and time-dependent manner. Flow cytometry showed that the cells were blocked at G_2/M phase and cell apoptosis was increased compared to the control. TSA significantly increased the acetyl level of histone H4, induced p21 and Bax expression, and inhibited the expression of cyclin BI and Bcl-2. Conclusion: TSA inhibits the growth of lung cancer cells in vitro through inducing cell apoptosis and cell cycle arrest, which might be related to its regulatory effects on the acetyl blot of histone and the expression of p21, Bax, Bcl-2 and cyclinBl.
ABSTRACT
Bone metastases in advanced lung cancer patients are common and affect the life quality seriously. So early diagnosis and appropriate treatments are important. The methods of diagnosis include X-ray, CT, MRI, ECT and PET, which are different in sensitivity and specificity. The gene microarray technique is another advance for detecting micrometastasis. The gene analysis also can help understanding the biological characteristics of the primary tumor. The treatment of bone metastases in lung cancer is various, including systemic and local therapeutic means. Surgery is often used to prevent or treat the compressions and bone fractures. Radiotherapy is one of the most effective methods of pain relief. Diphosphonate provides a new convenient and effective way of alleviative treatment. In addition, supportive and symptomatic treatments should be keep in mind.