Adenovirus-mediated expression of PML suppresses growth and tumorigenicity of prostate cancer cells

Dalin He, Zhao Mei Mu, Xiaofeng Le, Jer Tsong Hsieh, Rey Chen Pong, Leland W K Chung, Kun Sang Chang

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Abstract

Our previous studies demonstrated that the promyelocytic leukemia gene, PML, encodes a growth and transformation suppressor. Overexpression of PML inhibits cancer cell growth in vitro and in vivo. In this study, we further explored the possibility of applying PML as a potential agent for developing prostate cancer gene therapy using an adenovirus delivery system. We have constructed and produced the recombinant PML-adenovirus, Ad-PML in which the full-length PML cDNA is driven by the strong cytomegalovirus promoter. In LNCaP, DU145, and PC-3 prostate cancer cell lines, an infection efficiency of 90% can be achieved at a concentration of 2, 10, and 10 multiplicity of infection (MOI), respectively. Western blotting and immunofluorescence staining demonstrated that the AD-PML-infected cells expressed a high level of PML protein. The protein expression peaked at days 3-4 postinfection, and a detectable level of PML was found at day 18 after viral infection. To test the effect of Ad-PML on the growth of prostate cancer cells, the DU145 and LNCaP cells were infected with 10 and 2 MO1 of Ad-PML. We found that the growth rate of the Ad-PML-infected DU145 and LNCaP cells were significantly inhibited, A tumorigenicity test in nude mice showed that the Ad-PML-treated DU145 cells failed to form tumors. Most importantly, direct injection of Ad- PML into DU145-induced tumors was able to repress tumor growth in nude mice by 64%. Taken together, these data indicate that PML is a tumor growth suppressor in prostate cancer and that Ad-PML may he a potential candidate for human prostate cancer therapy.

Original languageEnglish (US)
Pages (from-to)1868-1872
Number of pages5
JournalCancer Research
Volume57
Issue number10
Publication statusPublished - May 15 1997

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

He, D., Mu, Z. M., Le, X., Hsieh, J. T., Pong, R. C., Chung, L. W. K., & Chang, K. S. (1997). Adenovirus-mediated expression of PML suppresses growth and tumorigenicity of prostate cancer cells. Cancer Research, 57(10), 1868-1872.