Replication-competent adenovirus (RCAd) has been used extensively in cancer gene therapy, and tumor-selection is critical for the use of replication-competent adenovirus.
Here we investigated the anti-tumor characterization of oncolytic virus, whose E1A gene is under the control of a renal cell carcinoma specific promoter - the G250 promoter. The constructed oncolytic virus G250-Ki67 is armed with transgene of Ki67-siRNA, and G250-ZD55-Ki67 also with E1B-55 KD deleted. The tumor-specific expression of E1A and Ki67 was demonstrated by Western blot and immunohistochemistry staining, and the tumor-specific cytotoxicity was assessed by crystal violet staining and cell viability assays. The G250-Ki67 and G250-ZD55-Ki67 adenoviruses could express E1A protein in 786-O and OSRC cell lines but not in ACHN and HK-2 cell lines. The expression of Ki67 gene in 786-O and OSRC cell lines were suppressed by these adenoviruses. The cytotoxic effects induced by G250-ZD55-Ki67 and G250-Ki67 were more obvious on the 786-O cell lines than on the OSRC cell lines. Each group of adenoviruses could inhibit the proliferation of the 786-O cells and OSRC cells. However, the effects induced by G250-ZD55-Ki67 and G250-Ki67 on 786-O cells were stronger than on OSRC cells. Moreover, G250-ZD55-Ki67 had enhanced antitumor activities in these renal cancer cells compared with G250-Ki67. G250 promoter-derived CRAds carrying Ki67-siRNA could highly amplify and express Ki67-siRNA in renal cancer cells with expression of G250 antigen, inhibit renal cancer cells proliferation and induce apoptosis. These results demonstrated that the G250-specific oncolytic adenovirus expressing Ki67-siRNA is applicable for human renal clear cell cancer therapy.
Written by:
Liu J, Fang L, Cheng Q, Li L, Su C, Zhang B, Pei D, Yang J, Li W, Zheng J. Are you the author?
Laboratory of Urology, Affiliated Hospital of Xuzhou Medical College, China.
Reference: Cancer Sci. 2012 Oct;103(10):1880-8.
doi: 10.1111/j.1349-7006.2012.02380.x
PubMed Abstract
PMID: 22775978
UroToday.com Investigative Urology Section
