Autor: |
Zhongshi Hong, Yachen Li, Mingliang Chen, Xiaojing Chen, Xian Deng, Yuze Wu, Chunxiao Wang, Chengzhi Qiu |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
Discover Oncology, Vol 15, Iss 1, Pp 1-15 (2024) |
Druh dokumentu: |
article |
ISSN: |
2730-6011 |
DOI: |
10.1007/s12672-024-01036-7 |
Popis: |
Abstract Background 5-fluorouracil (5-FU) is conventionally used in chemotherapy for colon adenocarcinomas. Acquired resistance of 5-FU remains a clinical challenge in colon cancer, and efforts to develop targeted agents to reduce resistance have not yielded success. Protosappanin B (PSB), the main component of Lignum Sappan extract, is known to exhibit anti-tumor effects. However, whether and how PSB could improve 5-FU resistance in colon cancer have not yet been established. In this study, we aimed to explore the effects and underlying mechanisms of PSB in 5-FU-induced chemoresistance in colon adenocarcinoma. Methods Forty-seven paired colon cancer tissue samples from patients who received 5-FU chemotherapy were collected as clinical samples. Two 5-FU resistant colon cancer cell lines were established for in vitro experiments. Reverse transcription-quantitative PCR (RT-qPCR) was performed to determine the mRNA and microRNA (miRNA) expression levels in colon adenocarcinoma tissues and cell lines. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were performed to evaluate cell proliferation and apoptosis, respectively. Results LINC00612 was highly expressed in colon adenocarcinoma samples and 5-FU resistant colon cancer cells. LINC00612 knockdown enhances 5-FU chemosensitivity in 5-FU resistant cells. Notably, PSB treatment attenuated LINC00612 expression in 5-FU resistant colon adenocarcinoma cells. Moreover, PSB treatment reversed the increase in LINC00612-induced 5-FU resistance. Mechanistically, LINC00612 specifically bound to miR-590-3p, which promoted 5-FU resistance in colon adenocarcinoma cells and attenuated the inhibitory effect of LINC00612 on GOLPH3 expression. Conclusion PSB attenuates 5-FU chemoresistance in colon adenocarcinoma by regulating the LINC00612/miRNA-590-3p/GOLPH3 axis. Graphical Abstract |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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