Jiacheng Tang1, Xiao Liang1, Rui Ma1, Jinghua Liu1, Xiaolong Liu1, Xiujun Cai2. 1. Key Lab of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, School Medicine, Zhejiang University, Hangzhou 310016, China. 2. Key Lab of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, School Medicine, Zhejiang University, Hangzhou 310016, China. Email: cxjzu@hotmail.com.
Abstract
OBJECTIVE: To explore the effects of autophagy on 5-fluorouracil (5-FU) cytotoxicity for gallbladder carcinoma GBC-SD cell and discuss a novel and promising strategy of autophagy inhibitor for increasing the clinical efficacy of 5-FU in the treatment of gallbladder carcinoma. METHODS: After a pre-treatment of autophagy inhibitors, such as chloroquine (CQ) and 3-methyladenine (3-MA), or silencing the autophagy-related genes (autophagy-related gene 5, autophagy-related gene 7), the inhibition of 5-FU to proliferation and the viability of GBC-SD cell were measured. And the apoptotic rate and cell cycle of GBC-SD cell were analyzed. RESULTS: Blocking of autophagy by pharmacological (CQ, 3-MA) or genetic (siRNA) means induced cell death in GBC-SD cell pre-treated with 5-FU.Furthermore, 5-FU treatment resulted in a general increase of apoptotic rate and G0/G1 arrest of GBC cells. And such an effect was potentiated by a pre-treatment of CQ. CONCLUSION: Autophagy in GBC-SD cell is induced by DNA damaging agent 5-fluorouracil.While in combination with CQ pre-treatment, the cytotoxicity of 5-fluorouracil becomes potentiated.
OBJECTIVE: To explore the effects of autophagy on 5-fluorouracil (5-FU) cytotoxicity for gallbladder carcinoma GBC-SD cell and discuss a novel and promising strategy of autophagy inhibitor for increasing the clinical efficacy of 5-FU in the treatment of gallbladder carcinoma. METHODS: After a pre-treatment of autophagy inhibitors, such as chloroquine (CQ) and 3-methyladenine (3-MA), or silencing the autophagy-related genes (autophagy-related gene 5, autophagy-related gene 7), the inhibition of 5-FU to proliferation and the viability of GBC-SD cell were measured. And the apoptotic rate and cell cycle of GBC-SD cell were analyzed. RESULTS: Blocking of autophagy by pharmacological (CQ, 3-MA) or genetic (siRNA) means induced cell death in GBC-SD cell pre-treated with 5-FU.Furthermore, 5-FU treatment resulted in a general increase of apoptotic rate and G0/G1 arrest of GBC cells. And such an effect was potentiated by a pre-treatment of CQ. CONCLUSION: Autophagy in GBC-SD cell is induced by DNA damaging agent 5-fluorouracil.While in combination with CQ pre-treatment, the cytotoxicity of 5-fluorouracil becomes potentiated.