Investigation of CEBPD's regulation and roles in drug-resistant bladder cancers

  • 王 韋然

Student thesis: Doctoral Thesis

Abstract

Urothelial carcinoma of urinary bladder (UCUB) is the fourth most common malignancy in men and the tenth most common in women Anticancer drug cisplatin (CDDP) is highly used in the therapy of UCUB In addition CDDP is frequently combination chemotherapy with paclitaxel (PTX) used in UCUB therapies However as well as other types of cancers the development of CDDP cross-resistance remains a challenge problem hindering the successful treatment of UCUB Therefore elucidating the mechanisms underlying CDDP-induced anticancer drug cross-resistance to develop novel strategies is urgent CCAAT/enhancer binding protein delta (CEBPD) is expressed at a relatively low level under normal physiological conditions and can be up-regulated by a variety of extracellular stimuli including IL-1β PGE2 TNF? and stress like as starvation of serum and anticancer drugs Actually the function of CEBPD is more than serves as a tumor suppressor; several reports suggested that CEBPD also play an oncogenic role in certain conditions For instance recent study have demonstrated that CDDP could induce CEBPD-mediated anti-apoptosis pathway in UCUB cells However how CDDP induces cross-resistance with PTX through transcription regulation of genes involved in anti-apoptosis remains largely unexplored In this study we found that the ABCB1 and ABCC2 genes were activated by CEBPD upon CDDP treatment The EGFR/STAT3 pathway contributed to the CDDP-induced CEBPD expression in the UCUB cells Both Gefitinib and S3I-201 significantly decreased CEBPD expression and enhanced the sensitivity of CDDP or PTX of CDDP-resistant NTUB1/P cells or NTUB1/P xenograft tumors Taken together our results demonstrate the risk of CEBPD activation in CDDP-resistant UCUB cells and suggest a potentially therapeutic strategy for treating patients with UCUB or UCUB with CDDP-induced PTX resistance via a combination of CDDP and Gefitinib or S3I-201
Date of Award2016 九月 29
語言English
SupervisorJu-Ming Wang (Supervisor)

引用此文

Investigation of CEBPD's regulation and roles in drug-resistant bladder cancers
韋然, 王. (Author). 2016 九月 29

Student thesis: Doctoral Thesis