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The effect of doxorubicin on p-glycoprotein expression during enterocytic differentiation of CACO-2 cells |
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| รหัสดีโอไอ | |
| Title | The effect of doxorubicin on p-glycoprotein expression during enterocytic differentiation of CACO-2 cells |
| Creator | Udomsak Udomnilobol |
| Contributor | Suree Jianmongkol |
| Publisher | Chulalongkorn University |
| Publication Year | 2558 |
| Keyword | Cancer cells -- Differentiation, Intestine, Large -- Cancer, Doxorubicin, ลำไส้ใหญ่ -- มะเร็ง, เซลล์มะเร็ง -- การเปลี่ยนสภาพ, ด็อกโซรูบิซิน |
| Abstract | Caco-2 cells are derived from human colon adenocarcinoma cells with an intrinsic expression of P-glycoprotein (P-gp). The differentiation phases might affect cellular redox status, reactive oxygen species (ROS) production, and cellular response to chemical threats. This study investigated the influence of the differentiation states of Caco-2 cells on cellular response at transcription level of ABCB1 gene toward doxorubicin treatment and the involvement of ROS. In this study, the differentiation states of Caco-2 cells were divided into three phases including the pre-, during-, and post-differentiation. The GSH/GSSG ratio apparently shifted to a more reduced state when the cells differentiated. Doxorubicin could affect ABCB1/P-gp expression at transcription level in Caco-2 cells at all growth states. An intracellular ROS level was significantly increased by doxorubicin treatment only in the pre-differentiated cells, which had an apparently more oxidized state than the cells in other phases. In the pre-differentiated cells, a known antioxidant N-acetylcysteine (NAC) was able to entirely inhibit ROS production, and partially inhibited upregulation of ABCB1 mRNA. In the during-differentiation phase, NAC potentially blocked doxorubicin-mediated upregulation of ABCB1 mRNA, but it had little effect on doxorubicin-mediated downregulation. In the post-differentiation phase, NAC had no effect on doxorubicin-mediated ABCB1 upregulation. In conclusion, the differentiation states of Caco-2 cells could determine the effect of doxorubicin on intracellular ROS level and ABCB1 gene expression. The ROS might take part in the mechanism of doxorubicin-mediated ABCB1 alteration at the transcription level in the pre- and the during-differentiation phases, but not in the post-differentiation state. It was likely that cellular redox status had an influence on ROS generated from doxorubicin. However, ROS was not the solely mechanism responsible for doxorubicin-mediated alteration of ABCB1 mRNA in Caco-2 cells at each differentiation state. |
| URL Website | cuir.car.chula.ac.th |
