Meloxicam executes its antitumor effects against hepatocellular carcinoma in COX-2- dependent and -independent...

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Cyclooxygenase (COX)-2 is overexpressed in hepatocellular carcinoma (HCC).
• Meloxicam, a selective COX-2 inhibitor, demonstrates potential therapeutic effects against HCC.
• The precise mechanisms of meloxicam's anti-cancer activity in HCC are not fully understood.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying meloxicam's anti-cancer effects in HCC.
• To investigate the roles of COX-2, apoptosis, and autophagy in meloxicam's action.
• To explore potential strategies for overcoming resistance to meloxicam treatment.

Main Methods:

• Investigated the effects of meloxicam on HCC cell migration, invasion, adhesion, and colony formation.
• Analyzed the expression of key proteins involved in apoptosis (Bax, Fas-L, survivin, Mcl-1) and autophagy (Beclin 1, light chain 3-II).
• Examined the role of AKT phosphorylation and prostaglandin E2 (PGE2) in meloxicam's mechanism of action.
• Assessed the impact of autophagy inhibition on meloxicam-induced apoptosis.

Main Results:

• Meloxicam inhibited HCC cell migration, invasion, adhesion, and colony formation by upregulating E-cadherin and downregulating matrix metalloproteinase (MMP)-2.
• Meloxicam induced apoptosis via both COX-2-dependent and -independent pathways, affecting apoptotic and anti-apoptotic proteins and inhibiting AKT phosphorylation.
• Meloxicam induced autophagy by upregulating Beclin 1 and light chain 3-II.
• Inhibition of autophagy enhanced meloxicam's pro-apoptotic effects.

Conclusions:

• Meloxicam exerts antitumor effects in HCC by targeting COX-2/MMP-2/E-cadherin, AKT, apoptotic, and autophagic pathways.
• These effects occur through both COX-2-dependent and -independent mechanisms.
• Inhibiting autophagy may be a strategy to enhance meloxicam's efficacy and overcome resistance in HCC treatment.