Page 88 - D. Cancer biology

[D. Cancer biology-58]

Significance of Jagged-1 activated by APEX1 as

chemoresistance factors in gastric cancer

HONG BEUM KIM¹

¹Department of Premedical Course, Chosun University School of Medicine, Gwangju 61453, Republic of Korea

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.