The Effect of Arsenic Trioxide and Its Combination with Oxaliplatin and Docetaxel on the Induction of Autophagy and Expression of LC3 and Beclin-1 Genes in AGS and MKN-45 Gastric Cancer Cell Lines.

Abstract

Purpose: Apoptosis and autophagy play critical roles in the survival and regulation of cancer cells, with key genes serving dual purposes in these processes. Arsenic trioxide (ATO), oxaliplatin (OXA), and docetaxel (DOC) are widely used in the treatment of various cancers. Specifically, ATO inhibits cellular proliferation and induces apoptosis in certain cancer cells, while OXA and DOC, common agents in cancer chemotherapy, continue to be actively studied for their potential therapeutic effects.

Methods: This study investigated the effects of ATO, DOC, and OXA on AGS and MKN-45 gastric cancer cell lines in vitro. The MTT assay was utilized to determine the effective concentrations of these compounds, both individually and in combination. Apoptosis was assessed using Annexin V-FITC staining, and the mRNA levels of genes related to autophagy and apoptosis were analyzed via real-time polymerase chain reaction (PCR).

Results: Our findings demonstrated that the combination of ATO with DOC and OXA significantly reduced the viability of AGS and MKN-45 cells compared to DOC or OXA therapy alone. Notably, the simultaneous administration of all three agents markedly enhanced apoptosis induction. Additionally, the combined use of two drugs showed a more pronounced impact on both cell necrosis and apoptosis compared to the effects of each drug used alone.

Conclusion: The combination of two therapeutic agents represents a promising strategy for inducing autophagy and gene expression related to apoptosis in gastric cancer cells. This approach exerted a more substantial influence on cell apoptosis and necrosis than single-drug treatments, underscoring its potential as an effective therapeutic option.