Heat shock and heat shock protein 70i enhance the oncolytic effect of replicative adenovirus

Citation
Ys. Haviv et al., Heat shock and heat shock protein 70i enhance the oncolytic effect of replicative adenovirus, CANCER RES, 61(23), 2001, pp. 8361-8365
Citations number
30
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
00085472 → ACNP
Volume
61
Issue
23
Year of publication
2001
Pages
8361 - 8365
Database
ISI
SICI code
0008-5472(200112)61:23<8361:HSAHSP>2.0.ZU;2-E
Abstract
Replication-competent viruses are currently being evaluated for their cance r cell-killing properties. These vectors are designed to induce tumor regre ssion after selective viral propagation within the tumor. However, replicat ion-competent viruses have not resulted heretofore in complete tumor eradic ation in the clinical setting. Recently, heat shock has been reported to pa rtially alleviate replication restriction on an avian adenovirus (Ad) in a human lung cancer cell line. Therefore, we hypothesized that beat shock and overexpression of heat shock protein (lisp) would support the oncolytic ef fect of a replication-competent human Ad. To this end, we tested the oncoly tic and burst kinetics of a replication-competent Ad after exposure to heat shock or to inducible lisp 70 overexpression by a replication-deficient Ad (Adhsp 70i). Heat-shock resulted in augmentation of Ad burst and oncolysis while decreasing total intracellular Ad DNA. Overexpression of lisp 70i al so enhanced Ad-mediated oncolysis but did not decrease intracellular Ad DNA levels. We conclude that heat shock and Adhsp 70i enhance the Ad cell-kill ing potential via distinct mechanisms. A potential therapeutic implication would be the use of local hyperthermia to augment oncolysis by increasing t he burst of replication-competent Ad. The role of lisp in Ad-mediated oncol ysis should be additionally explored.