PT - JOURNAL ARTICLE AU - HONG-BEUM KIM AU - HEE-JEONG LEE AU - GEE-BEUM KIM AU - HYUN-JONG LIM AU - JUN HEE PARK AU - SANG-GON PARK TI - Clinical Significance of Jagged-1 Activated by APEX1 as a Chemoresistance Factor in Advanced Gastric Cancer AID - 10.21873/anticanres.14144 DP - 2020 Apr 01 TA - Anticancer Research PG - 1897--1904 VI - 40 IP - 4 4099 - http://ar.iiarjournals.org/content/40/4/1897.short 4100 - http://ar.iiarjournals.org/content/40/4/1897.full SO - Anticancer Res2020 Apr 01; 40 AB - Background/Aim: We investigated the clinical role of the molecular targets, APEX1 and Jagged-1, and the Apex1 - Jagged-1 cascade in gastric cancer cells. Materials and Methods: We used 6 human gastric cancer cell lines (SNU-1, SNU-5, SNU-16, NCI-N87, KATO- III and AGS), and demonstrated the chemosensitivity of APEX1 and Jagged-1 through the MTT assay and immunoblotting. Tumor growth was assayed following cisplatin and 5-FU treatment using a xenograft model injected with KATO-III cells. Moreover, gastric tumor samples from 9 patients, divided in 2 groups according to chemotherapy response, were examined by immunocytochemical (IHC) staining, and protein expression levels were scored. Results: Following APEX1 knockdown, the MTT assay revealed that the IC50 of cisplatin and 5-FU in AGS cells was decreased approximately 7% and 15%, respectively, however, their decrease in chemoresistant KATO-III cells was decreased by approximately 21% and 67% for cisplatin and 5-FU, respectively. The tumor volume of KATO-III/sicontrol mice treated with cisplatin and 5-FU was affected less, compared with KATO-III/siAPEX1 mice treated with cisplatin and 5-FU. Also, the expression levels of APEX1, Jagged-1 and CD133, assayed by IHC staining, were higher in the chemorefractory group than in the chemoresponsive group. Conclusion: Jagged-1-activated signaling by APEX1 plays a role in advanced gastric cancer.