| Autor: |
Aravindan S; Department of Marine Sciences, Center of Advanced Study in Marine Biology, Annamalai University, Parangipettai, TN, India.; Stephenson Cancer Center, Oklahoma City, OK, USA., Ramraj S; Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Kandasamy K; Department of Marine Sciences, Center of Advanced Study in Marine Biology, Annamalai University, Parangipettai, TN, India., Thirugnanasambandan SS; Department of Marine Sciences, Center of Advanced Study in Marine Biology, Annamalai University, Parangipettai, TN, India., Somasundaram DB; Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Herman TS; Stephenson Cancer Center, Oklahoma City, OK, USA.; Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA., Aravindan N; Department of Radiation Oncology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. |
| Jazyk: |
angličtina |
| Zdroj: |
Oncotarget [Oncotarget] 2017 Jan 24; Vol. 8 (4), pp. 5717-5734. |
| DOI: |
10.18632/oncotarget.13900 |
| Abstrakt: |
Therapy-resistant pancreatic cancer (PC) cells play a crucial role in tumor relapse, recurrence, and metastasis. Recently, we showed the anti-PC potential of an array of seaweed polyphenols and identified efficient drug deliverables. Herein, we investigated the benefit of one such deliverable, Hormophysa triquerta polyphenol (HT-EA), in regulating the dissemination physiognomy of therapy-resistant PC cells in vitro,and residual PC in vivo. Human PC cells exposed to ionizing radiation (IR), with/without HT-EA pre-treatment were examined for the alterations in the tumor invasion/metastasis (TIM) transcriptome (93 genes, QPCR-profiling). Utilizing a mouse model of residual PC, we investigated the benefit of HT-EA in the translation regulation of crucial TIM targets (TMA-IHC). Radiation activated 30, 50, 15, and 38 TIM molecules in surviving Panc-1, Panc-3.27, BxPC3, and MiaPaCa-2 cells. Of these, 15, 44, 12, and 26 molecules were suppressed with HT-EA pre-treatment. CXCR4 and COX2 exhibited cell-line-independent increases after IR, and was completely suppressed with HT-EA, across all PC cells. HT-EA treatment resulted in translational repression of IR-induced CXCR4, COX2, β-catenin, MMP9, Ki-67, BAPX, PhPT-1, MEGF10, and GRB10 in residual PC. Muting CXCR4 or COX2 regulated the migration/invasion potential of IR-surviving cells, while forced expression of CXCR4 or COX2 significantly increased migration/invasion capabilities of PC cells. Further, treatment with HT-EA significantly inhibited IR-induced and CXCR4/COX2 forced expression-induced PC cell migration/invasion. This study (i) documents the TIM blueprint in therapy-resistant PC cells, (ii) defines the role of CXCR4 and COX2 in induced metastatic potential, and (iii) recognizes the potential of HT-EA in deterring the CXCR4/COX2-dependent dissemination destiny of therapy-resistant residual PC cells. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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