Meloxicam Inhibits Colon Cancer Cells Growth By Down-Regulation Of PI3K/AKT Signaling Pathway

Colorectal cancer (CRC) is the third most common malignancy and the second most common cause of cancer death despite diagnostic and treatment advances. Chemoprevention is likely to play a major approach to reduce adenoma risk and cancer-related mortality. Recently, epidemiological and laboratory data suggest that non-steroidal anti-inflammatory agents (NSAID) have antitumor effects. However, the biological mechanisms of NSAID for CRC treatment have not been fully elucidated. Meloxicam is a new generation of NSAIDs that specifically inhibit cyclooxygenase-2 (COX-2) activity and they are currently approved by the US Food and Drug Administration (FDA) for the treatment of arthritis. We select the meloxicam as the model drug to investigating the mechanism of NSAIDs on cell-proliferation and-apoptosis of CRC. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is the most common malignant tumor suppressor gene and it is a negative regulator of PI3K-Akt signaling pathway, affecting cells’proliferation, apoptosis, migration, genomic instability and metabolism. We treated LoVo cells with meloxicam then measured the proliferation, apoptosis, and the expression of PTEN. The LoVo cells model of nude-mice was used to evaluate the effect of meloxicam on CRC. Our results indicated that meloxicam has a chemoprevention and chemotherapeutic agent for CRC; Meloxicam could inhibit PI3K/AKT signaling transduction, which may be mediated by down-regulating the expression of PTEN.