title: Metabolic alteration--Overcoming therapy resistance in gastric cancer via PGK-1 inhibition in a combined therapy with standard chemotherapeutics.
abstract: OBJECTIVE
  It 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.
  
  
  METHODS
  All 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.
  
  
  RESULTS
  Using 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.
  
  
  CONCLUSIONS
  We 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.
authors: Clinic for Visceral, General and Transplant Surgery, Tuebingen University Hospital, Germany. Electronic address: carlcschneider@hotmail.de.
authors: Carl Christoph
authors: CC
authors: Schneider
authors: Clinic for Visceral, General and Transplant Surgery, Tuebingen University Hospital, Germany.
authors: Rami
authors: R
authors: Archid
authors: Clinic for Visceral, General and Transplant Surgery, Tuebingen University Hospital, Germany.
authors: Nathania
authors: N
authors: Fischer
authors: Institute for Clinical and Experimental Transfusion Medicine IKET, Tuebingen, Germany.
authors: Sarah
authors: S
authors: Bühler
authors: Department of Internal Medicine I, Medical University Hospital Tuebingen, Germany.
authors: Sascha
authors: S
authors: Venturelli
authors: Department of Internal Medicine I, Medical University Hospital Tuebingen, Germany.
authors: Alexander
authors: A
authors: Berger
authors: Department of Internal Medicine I, Medical University Hospital Tuebingen, Germany.
authors: Markus
authors: M
authors: Burkard
authors: Clinic for Visceral, General and Transplant Surgery, Tuebingen University Hospital, Germany.
authors: Andreas
authors: A
authors: Kirschniak
authors: Clinic for Visceral, General and Transplant Surgery, Tuebingen University Hospital, Germany.
authors: Robert
authors: R
authors: Bachmann
authors: Clinic for Visceral, General and Transplant Surgery, Tuebingen University Hospital, Germany.
authors: Alfred
authors: A
authors: Königsrainer
authors: Clinic for Visceral, General and Transplant Surgery, Tuebingen University Hospital, Germany.
authors: Jörg
authors: J
authors: Glatzle
authors: Clinic for Visceral, General and Transplant Surgery, Tuebingen University Hospital, Germany. Electronic address: derek.zieker@helios-kliniken.de.
authors: Derek
authors: D
authors: Zieker
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D000256:Adenoviridae; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D016685:Mitomycin / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D010735:Phosphoglycerate Kinase / Q000037:antagonists & inhibitors*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
chemical_list: D016685:Mitomycin; C577282:PGK1 protein, human; D010735:Phosphoglycerate Kinase; D005472:Fluorouracil
keywords: Combined in vitro therapy chemotherapeutics and adenovirus anti-PGK1; Human gastric adenocarcinoma cell line 23132/87; Metabolic alteration; PGK1; PGK1-inhibition; Therapy resistance in gastric cancer