Possible mechanisms of improved radiation response by cytotoxic RNase, Onconase, on A549 human lung cancer xenografts of nude mice.
The cytotoxic RNase, Onconase (ONC), isolated from amphibian oocytes, was used to study its effect on the radiation response in A549 human NSCLC in vitro and in vivo. In cell culture studies, we found that ONC increased the radiation response by ONC-induced inhibition of O2 consumption (QO2). The occurrence of apoptosis was increased by ONC and was dependent on dosages and time exposure (measured by a Tunnel in situ cell death detection assay). Moreover, ONC inhibited sublethal damage repair (SLDR), confirmed by a split dose experiment. In animal studies, ONC significantly increased the radiation-induced tumor growth delay of A549 tumors in vivo. Using a non-invasive DCE-MRI technology, ONC-induced changes of perfusion were observed in A549 tumors. We concluded that the ONC-induced enhancement in tumor oxygenation was mainly due to the reduction in QO2 rather than an increase in tumor blood flow. This investigation suggests important potential clinical uses of ONC for the treatment of NSCLC cancer patients.
Kim
Dae Hong
DH
Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kim
Eun Ju
EJ
Kalota
Anna
A
Gewirtz
Alan M
AM
Glickson
Jerry
J
Shogen
Kuslima
K
Lee
Intae
I
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012260:Ribonucleases / Q000494:pharmacology* / Q000627:therapeutic use; D014183:Transplantation, Heterologous
D000970:Antineoplastic Agents; D012260:Ribonucleases; C058703:ranpirnase