mechanism of lipid raft mediating chemoresistance of cervical cancer

ABSTRACT

To investigate the mechanism of lipid raft mediating chemotherapy resistance in cervical cancer. This experiment was carried out in the Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China from June 2010 to February 2011. Hela cells were divided into 6 groups control group [Ctrl], cisplatin group [Cis], lipid raft interference agent group [MCD], NADPH oxidase inhibitor group [Apo], lipid raft interference agent combined with cisplatin group [MCD+Cis], and NADPH oxidase inhibitor combined with cisplatin group [Apo+Cis]. After the cervical cancer cells were treated with a correspondent agent for 24 hours, the number of surviving cells were measured utilizing cell counting kits-8 [CCK-8], and the hypoxia inducible factor-1alpha [HIF-1alpha levels were detected by Western blotting. Reactive oxygen species [ROS] levels were measured indirectly by detection of dichlorodihydrofluorescein fluorescence activity. The cell growth of MCD slowed down [survival cells was 62% compared with the Ctrl group], with the Apo group showing a similar effect [65% in the control group], and 49% for the Cis group, MCD+Cis was 21%, and Apo+Cis was 23%. While the level of HIF-1alpha protein and ROS of the MCD group, Apo group, Cis group, MCD+Cis group and Apo+Cis group were decreased significantly compared to the control group. The level of HIF-1alpha of MCD group decreased by 69.9%, Apo group by 60.2%, Cis group was 55.5%, MCD+Cis group by 21.1% and Apo+Cis group by 25.4%, while the level of ROS also decreased in the MCD group by 38.6%, Apo group by 35.3%, Cis group by 24%, MCD+Cis group by 12.3% and Apo+Cis group by 12.8%. Lipid raft may up-regulate ROS level and HIF-1alpha expression through activating NADPH oxidase, and thus promote chemotherapy resistance in cervical cancer.