[Combination treatment with antisense oligonucleotides and chemotherapy in vitro].
Oncological therapy strategies are increasingly concentrating on the causal, molecular changes involved in carcinogenesis. So called "smart drugs" such as antisense oligoneucleotide (AsON) can be used as specific inhibitors of individual genes. AsONs have shown their effectiveness in many studies. Clinical studies have demonstrated, however, that for many tumours the inhibition of a single gene is, due to multigenetic alteration, largely ineffective. The combination of AsONs with conventional chemotherapeutic agents is currently being investigated in phase III studies. In these studies, chemotherapeutic agents have been evaluated in cell culture together with AsON against the proliferation associated Ki-67 gene, as well as against the apoptosis associated bcl-2 gene via RT-PCR, immunochemistry and MTT cell viability assay. For both AsONs, significant target inhibition was achieved in cell culture with a high target gene expression. The prior treatment of tumour cells with bcl-2 AsON significantly increased the effectiveness of chemotherapy, while the combination of conventional chemotherapeutic agents with Ki-67 AsON showed no synergistic effects.
Kausch
I
I
Klinik und Poliklinik für Urologie, Universitätsklinikum Schleswig-Holstein--Campus Lübeck. IKausch@aol.com
Ewerdwalbesloh
N
N
Jiang
H
H
Doehn
C
C
Krüger
S
S
Jocham
D
D
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D003124:Colorimetry; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D019394:Ki-67 Antigen / Q000235:genetics; D007680:Kidney Neoplasms / Q000473:pathology*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013873:Thionucleotides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D019394:Ki-67 Antigen; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D013873:Thionucleotides; C408162:oblimersen; D002945:Cisplatin