Antitumor activity of polyuridylic acid in human soft tissue and bone sarcomas.
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.


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.


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.


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.
Adepoju
Linda J
LJ
Department of Surgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
Geiger
James D
JD
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005354:Fibrosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008928:Mitochondria / Q000187:drug effects; D018317:Nerve Sheath Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011072:Poly U / Q000378:metabolism / Q000494:pharmacology*; D012208:Rhabdomyosarcoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D018227:Sarcoma, Clear Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051200:Toll-Like Receptor 8 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C495349:TLR8 protein, human; D051200:Toll-Like Receptor 8; D011072:Poly U; D020169:Caspases