Therapeutic potential of antisense oligodeoxynucleotides to down-regulate thymidylate synthase in mesothelioma

摘要: Malignant mesothelioma is an aggressive tumor of the serosal surfaces lungs, heart, and abdomen. Survival rates are poor effective treatments not available. However, recent therapeutic regimens targeting thymidylate synthase (TS) in malignant patients have shown promise. We reported use antisense oligodeoxynucleotide TS mRNA (antisense ODN 83) to inhibit growth human cells. To test potential for treatment mesothelioma, we assessed compared effects 83 on three cell lines (211H, H2052, H28) nonmalignant cells (HT29 colorectal adenocarcinoma, HeLa cervical carcinoma, MCF7 breast lines). report that applied as a single agent effectively reduced protein lines. Furthermore, it inhibited significantly more than lines: difference susceptibility was observed response with protein-targeting drugs. In cells, both induced apoptotic death proliferation. only proliferation observed. Thus, TS-mediated induction apoptosis may be basis high sensitivity TS. Further preclinical clinical study oligodeoxynucleotides, alone combination TS-targeting chemotherapy drugs, warranted.