TRIB3 as a biomarker of gastric cancer cell sensitivity to chemotherapeutic agents running title: A protective role of TRIB3 on chemotherapy.

Objectives: Understanding the role of TRIB3 in cellular chemotherapy responsiveness and survival could facilitate its development as a prognostic marker that could be used to improve chemotherapeutic efficiency against specific tumors. Therefore, the role of TRIB3 to reflect the cytotoxic abilities of chemotherapeutic agents was clarified in the tested gastric cancer cell lines.

Methods: We have comprehensively investigated the protein expression of TRIB3 in three gastric cancer cell lines AGS, TMK-1, and MKN-45 cells treated with the anticancer drugs, 5-fluorouracil, cisplatin, and docetaxel. The Cell Count kit-8 was used to evaluate cell viability. Immunoblotting was performed to assay protein levels after drug treatment. Flow cytometry was carried out to evaluate the levels of sub-G1 cell population.

Results: Treatment of the tested gastric cancer cell lines dose-dependently decreased cell viability and protein levels of TRIB3 while increasing apoptosis. Overexpression of TRIB3 protects MKN-45 cells from endoplasmic reticulum stress-induced apoptosis but does not influence the induction of autophagy by anticancer drugs. In addition, overexpression of TRIB3 also rescued paroxetine-induced apoptosis and endoplasmic reticulum stress.

Conclusions: Our previous and present results indicate that TRIB3 can protect gastric cancer cells against anticancer drug treatment and that downregulating TRIB3 may increase these cells' sensitivity to anticancer drugs. We thus suggest that the capability of anticancer drugs to downregulate TRIB3 can indicate tumors' potential susceptibility to these drugs.