What question did this study set out to answer?

The study aims to explore the synergistic effects of short-chain fatty acids combined with doxorubicin on gastric cancer cell proliferation.

January 10, 2026International Journal of Molecular Sciences0 citationsOpen Access

Postbiotics Combination Synergises the Antiproliferative Effects of Doxorubicin in Gastric Cancer Cells: A Cellular and Molecular Deep Dive

RERadwa A. EladwyWestern Sydney University MFMohamed FarèsThe University of Sydney MAMuhammad A. AlsherbinyCairo University

Key Result

The combination of short-chain fatty acids and doxorubicin enhanced cytotoxicity by 103.46% and increased apoptosis to 94.83% in gastric cancer cells.

Key Points

The study aims to explore the synergistic effects of short-chain fatty acids combined with doxorubicin on gastric cancer cell proliferation.
Utilized AGS gastric adenocarcinoma cells for testing cellular effects.
Measured IC50 values for doxorubicin and a combined SCFA mixture.
Analyzed apoptosis rates and necrosis in response to treatments.
Conducted proteomic profiling to assess molecular changes.
APB and doxorubicin inhibited cell proliferation, with respective IC50 values of 568.33 μg/mL and 0.22 μg/mL.
Combination treatment achieved 103.46% cell proliferation inhibition and lowered the APB IC50 to 512.80 μg/mL.
Confirmed synergistic interaction with combination index values of CI50 = 0.61.
Induced apoptosis in 94.83% of cells with only 4.64% necrosis.
Enhanced apoptosis-related pathways and stress responses through proteomic profiling.

Structured PICO

Does the combination of a short-chain fatty acid mixture and doxorubicin enhance antiproliferative effects in AGS gastric adenocarcinoma cells?

Population

AGS gastric adenocarcinoma cells

Intervention

Combined short-chain fatty acid mixture (APB) and doxorubicin (Dox)

Comparator

APB alone, Dox alone, or untreated control

Outcome

Antiproliferative synergy and cytotoxicitysurrogate

The combination of a short-chain fatty acid mixture and doxorubicin synergistically enhances cytotoxicity and apoptosis in gastric cancer cells, suggesting a potential strategy to potentiate chemotherapy efficacy.

Main Result

Absolute Event Rate: 0% vs 0%

Abstract

Short-chain fatty acids (SCFAs) acetate, propionate, and butyrate are microbial metabolites with recognised roles in gut and immune homeostasis, but their therapeutic relevance in gastric cancer, particularly in combination with chemotherapeutics, remains unclear. This study investigated the antiproliferative synergy between a combined SCFA mixture (APB) and doxorubicin (Dox) in AGS gastric adenocarcinoma cells using integrated cellular, molecular, and proteomic approaches. APB and Dox each inhibited cell proliferation, with IC50 values of 568.33 ± 82.56 μg/mL and 0.22 ± 0.04 μg/mL, respectively, and their combination (3000 + 0.27 μg/mL) enhanced cytotoxicity, achieving 103.46% inhibition and reducing the APB IC50 to 512.80 ± 18.37 μg/mL. Combination index values confirmed synergistic interactions (CI50 = 0.61; CI95 = 0.13). APB+Dox significantly increased apoptosis (94.83%) with minimal necrosis (4.64%) and induced strong ROS generation comparable to APB alone, while Dox showed limited oxidative effects. Proteomic profiling revealed downregulation of ribosomal proteins and cell cycle regulators in Dox and APB+Dox groups, with the combination further enhancing apoptosis-related pathways and stress responses. Overall, these findings indicate that SCFA-based interventions, exemplified by APB+Dox, may offer a low-toxicity strategy to potentiate chemotherapy efficacy in gastric cancer through apoptosis induction, redox disruption, and attenuation of drug resistance.

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