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Antitumor activity of polyuridylic acid in human soft tissue and bone sarcomas.
- Source :
-
The Journal of surgical research [J Surg Res] 2010 Nov; Vol. 164 (1), pp. e107-14. Date of Electronic Publication: 2010 Jun 09. - Publication Year :
- 2010
-
Abstract
- Background: The immunomodulatory properties of polyuridylic acid (PolyU) make it a promising agent in cancer immunotherapy. However, there is limited information on its direct effects on tumor cells.<br />Materials and Methods: TLR8 mRNA and protein expression in soft tissue sarcoma (STS) and bone sarcoma (BS) cell lines were determined by PCR and flow cytometry, respectively. Apoptosis and proliferation assays were performed using annexin V staining and BrdU incorporation assays, respectively. A relative cell enumeration was evaluated with WST-1 reagent. Expression levels of apoptotic proteins were evaluated by Western blotting.<br />Results: We demonstrate that PolyU treatment resulted in a significant decrease in STS and BS cell count by inducing apoptosis and inhibition of cell proliferation. All cell lines examined expressed TLR8 and the effect of PolyU was partially mediated through TLR8. Several apoptotic proteins including caspases were activated or increased in STS cells after treatment with PolyU. Administration PolyU resulted in significant growth inhibition of STS without any observable adverse effects in mouse xenograft tumor models.<br />Conclusions: These results elucidate the effect of PolyU in STS and BS cells and demonstrate that PolyU may be a potential therapeutic agent for STS and BS.<br /> (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antineoplastic Agents metabolism
Apoptosis drug effects
Bone Neoplasms metabolism
Bone Neoplasms pathology
Caspases metabolism
Cell Line, Tumor
Cell Survival drug effects
Fibrosarcoma metabolism
Fibrosarcoma pathology
Humans
Male
Mice
Mice, SCID
Mitochondria drug effects
Nerve Sheath Neoplasms drug therapy
Nerve Sheath Neoplasms metabolism
Nerve Sheath Neoplasms pathology
Osteosarcoma drug therapy
Osteosarcoma metabolism
Osteosarcoma pathology
Poly U metabolism
Rhabdomyosarcoma drug therapy
Rhabdomyosarcoma metabolism
Rhabdomyosarcoma pathology
Sarcoma, Clear Cell drug therapy
Sarcoma, Clear Cell metabolism
Sarcoma, Clear Cell pathology
Soft Tissue Neoplasms metabolism
Soft Tissue Neoplasms pathology
Toll-Like Receptor 8 metabolism
Xenograft Model Antitumor Assays
Antineoplastic Agents pharmacology
Bone Neoplasms drug therapy
Fibrosarcoma drug therapy
Poly U pharmacology
Soft Tissue Neoplasms drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1095-8673
- Volume :
- 164
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of surgical research
- Publication Type :
- Academic Journal
- Accession number :
- 20828720
- Full Text :
- https://doi.org/10.1016/j.jss.2010.05.038