Targeting of Topoisomerase I for Prognoses and Therapeutics of Camptothecin-Resistant Ovarian Cancer
| Autor: | Chien Shu Chen, Chii Hong Lee, Jaulang Hwang, Hsiang Ping Tsai, Jen Chine Wu, Yu Chieh Lee, Herng Wei An, Phui Ly Leiw, Chun Mao Lin, Shih Hao Huang, Kur Ta Cheng, Chi-Ming Lee, Chi Long Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
endocrine system
endocrine system diseases Colorectal cancer medicine.medical_treatment lcsh:Medicine Apoptosis Indole Alkaloids Mice Cell Line Tumor medicine Animals Humans lcsh:Science Cancer staging Ovarian Neoplasms Chemotherapy Multidisciplinary TUNEL assay biology Topoisomerase lcsh:R Cell Cycle medicine.disease Molecular biology Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays Treatment Outcome Terminal deoxynucleotidyl transferase DNA Topoisomerases Type I Drug Resistance Neoplasm biology.protein Cancer research lcsh:Q Camptothecin Female Ovarian cancer medicine.drug Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 7, p e0132579 (2015) |
| ISSN: | 1932-6203 |
| Popis: | DNA topoisomerase I (TOP1) levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the mechanisms associated with the development of camptothecin (CPT) resistance in ovarian cancers and identified evodiamine (EVO), a natural product with TOP1 inhibiting activity that overcomes the resistance. The correlations among TOP1 levels, cancer staging, and overall survival (OS) were analyzed. The effect of EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was associated with poor prognosis in ovarian cancers (p = 0.024). EVO induced apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The tumor size decreased significantly in the EVO treatment group compared with the control group (p < 0.01) in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be developed as an antiproliferative agent for overcoming CPT resistance in ovarian cancers. |
| Databáze: | OpenAIRE |
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