Original researchMetabolic alteration - Overcoming therapy resistance in gastric cancer via PGK-1 inhibition in a combined therapy with standard chemotherapeutics

- Role of PGK1 in metastatic spread of gastric carcinomas and influence on tumor stem cells.
- Inhibition of PGK1 via adenovirus-shPGK1.
- PGK1-inhibition is able to increase the vulnerability of gastric cancer cells and tumor stem cells.
- PGK1-inhibition may be a new way to overcome the chemotherapeutic therapy resistance.

Background and ObjectivesIt can be assumed that PGK1 is involved in metastatic spread of gastric carcinomas. Furthermore PGK1 has a proven influence on the characteristics of tumor stem cells. The presence of malignant stem cells, regarding treatment resistance and recurrence, is of considerable importance. We hypothesized that inhibition of PGK1 makes these cells more sensitive to chemotherapeutic agents and therefore mediates an overcome of the existing therapy resistance.MethodsAll investigations were performed with human gastric adenocarcinoma cell lines. Small hairpin RNA knockdown of PGK1 via adenovirus-shPGK1 was used for PGK1-inhibition. Chemotherapeutic agents were 5-FU and mitomycin. FACS, qRT-PCR, and xCELLigence were performed.ResultsUsing the medium-sole-control indicating the highest cell viability and Triton indicating the lowest, mitomycin and 5-FU alone showed a significant decrease in cell viability. The treatment with AdvshPGK1 alone already showed a better decrease. The simultaneous application of chemotherapeutics and adenovirus showed the strongest effect and is comparable to the effect of Triton.ConclusionsWe showed a significant decrease in cell viability after the simultaneous application of chemotherapeutics and adenovirus. These results suggest that PGK1-inhibition is able to increase the vulnerability of gastric cancer cells and tumor stem cells to overcome the chemotherapeutic therapy resistance.