[Effects of autophagy on 5-fluorouracil cytotoxicity for gallbladder carcinoma GBC-SD cell].
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.


CONCLUSIONS
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.
Key Lab of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, School Medicine, Zhejiang University, Hangzhou 310016, China.
Jiacheng
J
Tang
Key Lab of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, School Medicine, Zhejiang University, Hangzhou 310016, China.
Xiao
X
Liang
Key Lab of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, School Medicine, Zhejiang University, Hangzhou 310016, China.
Rui
R
Ma
Key Lab of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, School Medicine, Zhejiang University, Hangzhou 310016, China.
Jinghua
J
Liu
Key Lab of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, School Medicine, Zhejiang University, Hangzhou 310016, China.
Xiaolong
X
Liu
Key Lab of Surgery of Zhejiang Province, Sir Run Run Shaw Hospital, School Medicine, Zhejiang University, Hangzhou 310016, China. Email: cxjzu@hotmail.com.
Xiujun
X
Cai
D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002738:Chloroquine / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans
D002738:Chloroquine; D005472:Fluorouracil