AB26. Regulatory mechanism of ZNF139 in multidrug resistance of gastric cancer cells

Background and aim: Zinc finger protein 139 (ZNF139) is a member of zinc finger protein family with transcription function. Some members in zinc finger protein family are closely related to tumorigenesis, development and multidrug resistance (MDR) in tumors. Our previous study found increased ZNF139 expression in gastric cancer (GC) cells, which was related to tumor differentiation. However, the mechanism is still unclear. Purpose of the study is to further clarify the role and mechanism of ZNF139 in MDR of GC cells.

Methods: MTT assay, reverse transcription- polymerase chain reaction (RT-PCR), Western blotting were employed to test different differentiated GC tissues and well differentiated GC cell line MKN28, poorly differentiated GC cell line MGC803, to detect susceptibility of GC cells to chemotherapeutic agents (5-FU, L-OHP) in vitro, and expressions of ZNF139 and MDR associated genes MDR1/P-gp, MRP1, Bcl-2 and Bax were also detected. siRNA specific to ZNF139 was transfected into MKN28 cells, and then in vitro chemosensitivity of GC cells as well as changes of ZNF139 and MDR1/P-gp, MRP1, Bcl-2 and Bax were detected before and after transfection.

Results: The inhibition rate of chemotherapy drugs (5-FU, L-OHP) to well-differentiated GC tissues and cell line was lower than that in the poorly differentiated tissues and cell lines; expressions of ZNF139 and MDR1/P-gp, MRP1 and Bcl-2 in well-differentiated GC tissues and cell line MKN28 were higher, while Bax expression was lower than those in the poorly differentiated GC tissues and cell line SGC803 in mRNA and protein levels. After ZNF139-siRNA was transfected into MKN28, ZNF139 expression in GC cells was inhibited by 90%; inhibition rate of chemotherapeutic agents (5-FU, L-OHP) to tumor cells was increased, while expressions of MDR1/P-gp, MRP1 and Bcl-2 were down-regulated, and Bax was up-regulated (all P

Conclusions: MDR characteristics of GC cells could be reversed by inhibiting expression of ZNF139; ZNF139 was involved in GC MDR by promoting expressions of MDR1/P-gp, MRP1 and Bcl-2 and inhibiting Bax simultaneously.

Keywords: Gastric cancer; zinc finger protein 139; cells, differentiation; multidrug resistance, reversal