AQP5 silencing suppresses p38 MAPK signaling and improves drug resistance in colon cancer cells
| Autor: | Junjie Dong, Lei Tang, Wei Zhao, Yong-bin Yang, Xiao-ming Shi, Yüexin Wang, Bo-Nan Lü, Shengchun Wu, Guangwei Jiang |
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| Rok vydání: | 2014 |
| Předmět: |
MAPK/ERK pathway
Colorectal cancer Organic Anion Transporters Biology p38 Mitogen-Activated Protein Kinases medicine Humans ATP Binding Cassette Transporter Subfamily B Member 1 Protein kinase A Protein kinase B Cisplatin Kinase Cancer Thymidylate Synthase General Medicine medicine.disease Molecular biology Aquaporin 5 Gene Expression Regulation Neoplastic DNA Topoisomerases Type II Gene Knockdown Techniques Colonic Neoplasms Cancer research Fluorouracil Signal transduction HT29 Cells Signal Transduction medicine.drug |
| Zdroj: | Tumor Biology. 35:7035-7045 |
| ISSN: | 1423-0380 1010-4283 |
| Popis: | It is known that aquaporin 5 (AQP5) may represent a novel therapeutic target for treating colon cancer (CC), but whether AQP5 plays a role in the regulation of multidrug resistance (MDR) of colon cancer still remains unclear. In the present study, AQP5 and P-glycoprotein (P-gp), glutathione S-transferase-π (GST-π), topoisomerase II (TOPO II), and thymidylate synthase (TS) were checked in CC and adjacent cancer tissues; AQP5-siRNA was applied to silencing AQP5 in CC cell line HT-29, 5-fluorouracil (5-FU), and cisplatin (DDP) added on cells, and sulforhodamine B (SRB) was used; fluorescence real-time quantitative RT-PCR and Western blot were employed to detect changes in multidrug resistance factor and expression mitogen-activated protein kinase (MAPK) signaling pathway in HT-29. The results showed that AQP5 is significantly induced in cancer tissues than that in adjacent cancer tissues. The expression of AQP5 is positively correlated with drug resistance factors, as demonstrated by the increased expressions of P-gp, GST-π, and TOPO II in CC tissues compared to that in adjacent cancer tissues. Conversely, knockdown of AQP5 in HT-29 human colon cancer cells increased inhibition rates of cancer chemotherapeutic drugs such as 5-FU and DDP. The improved efficacies of chemotherapeutic drugs are associated with the decreased expression of P-gp, GST-π, and TOPO II. In addition, phosphorylation of p38 MAPK was increased by knockdown of AQP5 in HT-29 cells while phosphorylation and expression of extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and Protein kinase B (AKT) were not affected. P38 MAPK inhibitor increased the drug sensitivity of HT-29 cells in a similar way as AQP5-siRNAs do. So these results indicate that AQP5 is associated with drug resistance of colon cancer, and that the AQP5-P38 MAPK pathway may represent a potential drug target to improve drug resistance of colon cancer cells. |
| Databáze: | OpenAIRE |
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