Page 20 - D. Cancer biology

[D. Cancer biology-15]

Catechin senstize 5-fluorouracil resistance in gastric cancer

cells through inhibiting lactae dehydrogenase

Jung Ho Han¹, Bo-Sung Kim¹, Ling Jin¹, Yoonju Do¹, Dongryeol Ryu², In-Kyu Lee³, Ki-Tae Ha¹˙*

¹Korean Medical Science, Pusan National University, Yangsan 50612, Republic of Korea, ²Molecular Cell Biology,

Sungkyunkwan University, Suwon 16419, Republic of Korea, ³Internal Medicine, Kyungpook National University,
Daegu 41566, Republic of Korea

Resistance to the therapeutic drug occurs virtually every type of anti-cancer drugs. 5-fluorouracil (5-FU) is anti-

cancer therapy for gastric cancer however, its effectiveness is getting limited owing to drug resistance. In recent,

Warburg’s effect, a preference of glycolysis rather than OxPhos even in an oxygen-rich environment, is accepted as
a pivotal mechanism regulating the resistance to chemotherapy. Thus, we investigated the detailed mechanism
using established gastric cancer cell lines, SNU620 and SNU620/5FU. SNU620/5FU, a gastric cancer cells harboring

resistance 5-FU, showed higher expressions of glycolysis-related enzymes, such as lactate dehydrogenase A (LDHA),
pyruvate dehydrogenase kinase (PDK) -2, and PDK-3, compared to that of the parent cell, SNU620. To limits the

glycolysis, we examined the catechin, famous anti-inflammatory and anti-cancer natural products. Catechin has an
inhibitory effect on Lactate production and LDHA activity, but not PDKs. Also, the combination of 5-FU and catechin

showed a synergistic cytotoxicity on SNU620 / 5FU cells by ROS-mediated apoptosis. From these results, we suggest
catechin as a candidate for developing a novel adjuvant drug reducing chemo-resistance to 5-FU through restricting

LDHA.