Inhibition of PC-3 prostate cancer cell growth in vitro using both antisense oligonucleotides and taxol.
Antisense oligonucleotides (oligos) directed against mRNA-encoding transforming growth factor-alpha (TGF-alpha) and the epidermal growth factor receptor (EGFR) have demonstrated in vitro and in vivo efficacy against prostate cancer tumor models. However, many therapeutic agents have increased effectiveness when given in combination with other more established agents. We evaluated the effectiveness of two oligos (3.32 and 6.64 microM/L) known to have significant activity against the PC-3 prostate cell line in combination therapy with the chemotherapeutic agent paclitaxel (Taxol) (2.5 and 5.0 nm). Therapy was evaluated when oligos and Taxol were administered either as (1) single agents, (2) simultaneously in a combined therapy, or (3) sequentially, a form of combination therapy with both agents being administered in a series. We found that when either of the two oligos were given simultaneously with Taxol, no synergistic activity was noted. However, when sequentially administered in a series 1 d apart, a pretreatment with the antisense directed against TGF-alpha (6.64 microM/L) followed by Taxol (5 nm) had significantly greater activity than these agents similarly administered in the reverse order or simultaneously.>
Rubenstein
Marvin
M
Division of Cellular Biology, Hektoen Institute for Medical Research, Chicago, IL, USA. DrMarv@Prodigy.net
Slobodskoy
Leonid
L
Mirochnik
Yelena
Y
Guinan
Patrick
P
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004357:Drug Synergism; D066246:ErbB Receptors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage*; D017239:Paclitaxel / Q000008:administration & dosage*; D010714:Phosphatidylethanolamines / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D012334:RNA, Neoplasm / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000235:genetics*; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D016376:Oligonucleotides, Antisense; D010714:Phosphatidylethanolamines; D012334:RNA, Neoplasm; D016211:Transforming Growth Factor alpha; C020888:1,2-dielaidoylphosphatidylethanolamine; D066246:ErbB Receptors; D017239:Paclitaxel