Effect of aldosterone on the amplification of oncolytic vaccinia virus in human cancer lines

• Published in: Clinical and molecular hepatology Vol. 17; no. 3; pp. 213 - 219
• Main Authors: Lee, Hyun Ju, Rho, Jasung, Gui, Shao Ran, Kim, Mi Kyung, Lee, Yu Kyoung, Lee, Yeon Sook, Kim, Jeong Eun, Cho, Euna, Cho, Mong, Hwang, Tae-Ho
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Association for the Study of the Liver 01.09.2011; The Korean Association for the Study of the Liver; 대한간학회
• Subjects: Adrenal glands; Aldosterone - pharmacology; Amiloride - analogs & derivatives; Amiloride - pharmacology; Animals; Ascites; Cancer; Carcinoma, Hepatocellular - blood; Carcinoma, Hepatocellular - virology; Cell Line, Tumor; Edema; Gene expression; Hormones; Humans; Hydrocortisone - blood; Hydrogen-Ion Concentration; Infections; Liver Neoplasms - blood; Liver Neoplasms - virology; Mineralocorticoid Receptor Antagonists - pharmacology; Neuroprotective Agents - pharmacology; Oncolytic Virotherapy; Original; Patients; Rabbits; Signal transduction; Spironolactone - pharmacology; Vaccinia virus - drug effects; Vaccinia virus - genetics; Vaccinia virus - metabolism; Vaccinia virus - physiology; Virus Replication - drug effects; Viruses; 내과학; United States > US; Germany
• ISSN: 1738-222X; 2287-2728; 2093-8047; 2093-8047; 2287-285X
• DOI: 10.3350/kjhep.2011.17.3.213

JX-594 is an oncolytic virus derived from the Wyeth vaccinia strain that causes replication-dependent cytolysis and antitumor immunity. Starting with a cross-examination of clinical-trial samples from advanced hepatocellular carcinoma patients having high levels of aldosterone and virus amplification in JX-594 treatment, we investigated the association between virus amplification and aldosterone in human cancer cell lines. Cell proliferation was determined by a cell-counting-kit-based colorimetric assay, and vaccinia virus quantitation was performed by quantitative polymerase chain reaction (qPCR) and a viral plaque assay. Also, the intracellular pH was measured using a pH-sensitive dye. Simultaneous treatment with JX-594 and aldosterone significantly increased viral replication in A2780, PC-3, and HepG2 cell lines, but not in U2OS cell lines. Furthermore, the aldosterone treatment time altered the JX-594 replication according to the cell line. The JX-594 replication peaked after 48 and 24 hours of treatment in PC-3 and HepG2 cells, respectively. qPCR showed that JX-594 entry across the plasma membrane was increased, however, the changes are not significant by the treatment. This was inhibited by treatment with spironolactone (an aldosterone-receptor inhibitor). JX-594 entry was significantly decreased by treatment with EIPA [5-(N-ethyl-N-isopropyl)amiloride; a Na(+)/H(+)-exchange inhibitor], but aldosterone significantly restored JX-594 entry even in the presence of EIPA. Intracellular alkalization was observed after aldosterone treatment but was acidified by EIPA treatment. Aldosterone stimulates JX-594 amplification via increased virus entry by affecting the H(+) gradient.