Starvation-Induced Differential Virotherapy Using an Oncolytic Measles Vaccine Virus.
Viruses
; 11(7)2019 07 05.
Article
en En
| MEDLINE
| ID: mdl-31284426
ABSTRACT
Starvation sensitizes tumor cells to chemotherapy while protecting normal cells at the same time, a phenomenon defined as differential stress resistance. In this study, we analyzed if starvation would also increase the oncolytic potential of an oncolytic measles vaccine virus (MeV-GFP) while protecting normal cells against off-target lysis. Human colorectal carcinoma (CRC) cell lines as well as human normal colon cell lines were subjected to various starvation regimes and infected with MeV-GFP. The applied fasting regimes were either short-term (24 h pre-infection) or long-term (24 h pre- plus 96 h post-infection). Cell-killing features of (i) virotherapy, (ii) starvation, as well as (iii) the combination of both were analyzed by cell viability assays and virus growth curves. Remarkably, while long-term low-serum, standard glucose starvation potentiated the efficacy of MeV-mediated cell killing in CRC cells, it was found to be decreased in normal colon cells. Interestingly, viral replication of MeV-GFP in CRC cells was decreased in long-term-starved cells and increased after short-term low-glucose, low-serum starvation. In conclusion, starvation-based virotherapy has the potential to differentially enhance MeV-mediated oncolysis in the context of CRC cancer patients while protecting normal colon cells from unwanted off-target effects.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inanición
/
Vacuna Antisarampión
/
Viroterapia Oncolítica
/
Antineoplásicos
Límite:
Humans
Idioma:
En
Revista:
Viruses
Año:
2019
Tipo del documento:
Article
País de afiliación:
Alemania