Abstract
Autophagy1 is a complex of adaptive cellular response that enhances cancer cell survival in the face of cellular stresses such as chemothery. Here we show that in human gallbladder carcinoma (GBC) cells lines, SGC-996 and GBC-SD, autophagy is induced by the DNA damaging agent 5-fluorouracil (5-FU). While in combination with the pre-treatment of chloroquine (CQ), a inhibitor of autophagy, the inhibition of 5-FU to the proliferation and viability of GBC cells was potentiated. Furthermore, 5-FU treatment resulted in a general increase of the apoptotic rate and G0/G1 arrest of GBC cells, and the effect was potentiated by CQ pre-treatment. Since 5-FU induced autophagy in GBC cells, and CQ inhibited autophagy, our findings suggest a possible mechanism that CQ inhibited 5-FU-induced autophagy, which modified the cytotoxicity of 5-FU. The combination therapy of CQ and 5-FU should be considered as an effective strategy for the treatment of gallbladder carcinoma.
Highlights
To improve cancer cure rates, understanding of the mechanisms of the anticancer agents, as well as the mechanisms of acquisition of chemoresistance by cancer cells, is essential
We aimed to investigate the effects of the combination of chemotherapy with CQ on two kinds of gallbladder-carcinoma-derived cells, namely SGC-996 and gallbladder carcinoma (GBC)-SD. 5-FU is one of the major antitumor agents widely used against cancer for about 40 years
(See figure on previous page.) Figure 4 CQ potentiates apoptosis of SGC cells induced by 5-FU. (A) The population of annexin V+ apoptotic cells were evaluated by FCM using annexin V-FITC/PI staining in SGC-996 cells and GBC-SD cells after CQ-pretreatment at 100 μM for 12 hours, followed by 5-FU at 5 μM for 48 hours
Summary
To improve cancer cure rates, understanding of the mechanisms of the anticancer agents, as well as the mechanisms of acquisition of chemoresistance by cancer cells, is essential. Primary gallbladder carcinoma is one of the most common malignancies of the digestive tract in china and has been increasing incidence worldwide [1]. In the majority of cases, the diagnosis of this carcinoma is usually made postoperatively on tumors at an advanced stage, resulting in a 5-year survival rate of
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