Background: Gastric cancer represents one of the most formidable challenges in
public health and remains a leading cause of malignancy-related mortality
worldwide. Despite significant diagnostic advancements, conventional
chemotherapy protocols—particularly those based on 5-Fluorouracil (5-Fu)—
frequently encounter severe limitations in clinical efficacy due to the development
of acquired drug resistance and profound systemic toxicity.
Consequently, "Combination Therapy" strategies, utilizing natural bioactive
compounds to enhance the sensitivity of tumor cells while reducing the required
dosage of synthetic chemotherapeutics, have garnered substantial attention. The
present study was designed and conducted to evaluate the synergistic effects of the
natural flavonoid Quercetin (Que) in combination with 5-Fu on the gastric cancer
cell line (AGS), and to elucidate the underlying molecular mechanisms governing
this interaction.
Methodology: In this in vitro study, the cytotoxicity of various concentrations of
Quercetin (50–400 μM) and 5-Fluorouracil (5–80 μM) was determined at 24 and
48 hours using the MTT assay. Following the determination of optimal dosages (½
IC50), the apoptosis induction rate was evaluated via Annexin V/PI flow cytometry,
and the migratory potential of the cells was assessed through the Scratch (Wound
Healing) assay. Furthermore, to investigate the underlying molecular mechanisms,
the expression levels of key genes, including lncRNA-MALAT1, Bax, and Bcl-2,
were quantified using the Real-time PCR technique.
Results: The results demonstrated that the combination of Que and 5-Fu at sublethal concentrations significantly reduced the viability of AGS cells and increased
the rate of programmed cell death compared to monotherapy through synergistic
interactions. Findings from the scratch assay confirmed that this pharmacological
intervention, in addition to inducing apoptosis, severely restricted the migratory and
invasive potential of cancer cells by di