NS398 induces apoptosis in non-small cell lung cancer cells.

Abstract

PURPOSE:

Non-steroidal anti-inflammatory drugs (NSAIDs) can induce the apoptosis of many tumor cells and inhibit their growth. NS398 is an NSAID that inhibits COX-2 expression and induces tumor apoptosis via other pathways. The current study aims to observe the effects of NS398 on A549 cell apoptosis and investigate the apoptosis mechanism.

METHODS:

The A549 cells were treated with different NS398 concentrations. The growth inhibition of A549 cell was analyzed via a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and morphologic alterations were observed to detect apoptosis. The expression of survivin and caspase-3 mRNA was quantified via reverse transcriptase polymerase chain reaction, and the expression of caspase-3 and p-AKT protein was detected via western blot analysis.

RESULTS:

The MTT results show that NS398 inhibits A549 cell growth. The inhibition rate of NS398 (400 μmol/L) on A549 cells is up to 66.95% after 48 h of treatment. Simultaneously, the morphology experiment revealed significant apoptotic characteristics in A549 cells, such as green nuclear plasmid and different degrees of nuclear fragmentation. The expression of survivin mRNA was significantly reduced (P < 0.05, P < 0.01, and P < 0.001) and that of caspase-3 mRNA was significantly increased (P < 0.05 and P < 0.001) in the group treated with NS398 for 24 h in a dose-dependent manner. On the other hand, survivin and p-AKT were expressed at low levels (P < 0.01 and P < 0.001) and caspase-3 was increased significantly (P < 0.05 and P < 0.001) in the group treated with NS398 for 48 h in a dose-dependent manner.

CONCLUSION:

The current study proves that NS398 induces apoptosis in A549 cells, thereby inhibiting tumor growth. This function of NS398 may be related to the inhibition of AKT phosphorylation and survivin protein downregulation.

• Authors: Rong Qiu, Jian Chen, Jun Sima, Xiangdi Shen, Dandan Liu, Jian Shen
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 138 Issue 1 Pg. 119-24 (Jan 2012) ISSN: 1432-1335 [Electronic] Germany
• PMID: 22048655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BIRC5 protein, human
• Cyclooxygenase 2 Inhibitors
• Inhibitor of Apoptosis Proteins
• Nitrobenzenes
• Sulfonamides
• Survivin
• N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
• Oncogene Protein v-akt
• Caspase 3

Topics

• Apoptosis (drug effects)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, pathology)
• Caspase 3 (biosynthesis)
• Cell Growth Processes (drug effects)
• Cell Line, Tumor
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Dose-Response Relationship, Drug
• Humans
• Inhibitor of Apoptosis Proteins (biosynthesis)
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Nitrobenzenes (pharmacology)
• Oncogene Protein v-akt (biosynthesis, metabolism)
• Phosphorylation
• Sulfonamides (pharmacology)
• Survivin