br B Lomonte Y Angulo C Santamaria Comparative study
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Antitumor effect of a dual cancer-specific oncolytic adenovirus on prostate cancer PC-3 cells
b Institute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun, P. R. China c Changchun University of Chinese Medicine, Changchun, P. R. China d Department of Operating Room, The Second Hospital of Jilin University, Changchun, Jilin, P. R. China
e Jiang su Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, P. R. China f Department of Urology Surgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, P. R. China
Purpose: Apoptin can specifically kill cancer PFK-158 but has no toxicity to normal cells. Human telomerase reverse transcriptase (hTERT) acts as a tumor-specific promoter, triggering certain genes to replicate or express only in tumor cells, conferring specific replication and killing abili-ties. This study aimed to investigate the anticancer potential of the recombinant adenovirus Ad-apoptin-hTERTp-E1a (Ad-VT) in prostate cancer.
Methods: The pGL4.51 plasmid was used to transfect PC-3 cells to construct tumor cells stably expressing luciferase (PC-3-luc). Crystal violet staining and MTS assays determined the ability of Ad-VT to inhibit cell proliferation. Ad-VT-induced apoptosis of PC-3-luc cells was detected using Hoechst, Annexin V, JC-1 staining, and caspases activity analysis. PC-3-luc cells invasion and migration were detected using cell-scratch and Transwell assays. In vivo tumor inhibition was detected using imaging techniques.
Results: Crystal violet staining and MTS results showed that the proliferation ability of PC-3-luc cells decreased significantly. Hoechst, JC-1, and Annexin V experiments demonstrated that Ad-VT mainly induced apoptosis to inhibit PC-3-luc cell proliferation. Ad-VT could significantly inhibit the migration and invasion of PC-3-luc cells over a short period of time. In vivo, Ad-VT could effectively inhibit tumor growth and prolong survival of the mice.
Conclusions: The recombinant adenovirus, comprising the apoptin protein and the hTERTp promoter, was able to inhibit the growth of prostate cancer PC-3 cells and promote their apoptosis. 2018 Elsevier Inc. All rights reserved.
Keywords: Apoptin; hTERT; Recombinant adenovirus; PC-3-luc cells
Prostate cancer is the most common malignant tumor of the male genitourinary system. It is an epithelial malignant tumor , and has a high morbidity and mortality [2−4]. Prostate cancer is the most common malignant tumor of the male genitourinary system. It is a malignant epithelial tumor, with high morbidity and mortality rates. In United States, most commonly diagnosed cancer in men is prostate
cancer, with newly 161,360 people were diagnosed in 2017 [5,6]. In recent years, the incidence of prostate cancer in China has significantly increased. Prostate cancer has become one of the malignancies that threaten men world-wide . Currently, the treatment options for prostate cancer are including surgery, combinatorial chemotherapy, immunotherapy, and radiotherapy. However, these treat-ment options have significant limitations such as low cura-tive effect, causing large necrotic areas, and serious side effects. In addition, there is no targetable drug presented in clinics. The hotspot of current research in prostate cancer is to find better effective drugs with low side-effects.
By the widespread usage of genetic engineering in biol-ogy and in medicine, gene targeted therapies have become possible for cancer management. Gene therapy has shown prominent advantage, and the study found that the virus has great potential in cancer treatment . Oncolytic virus ther-apy is an oncolytic virus that has the function of targeting and killing tumor cells by selecting some strains with weak pathogenicity in nature or by objective genetic modification of certain viruses . At present, there are dozens of onco-lytic viruses for tumor treatment, including adenovirus, type I simple herpes virus, Newcastle disease virus, vac-cinia virus, reovirus, and vesicular stomatitis virus . The treatment using adenovirus as a carrier to target cancer cells, has received extensive research attention and has become a research hotspot. Adenovirus therapy is expected to replace traditional therapy for cancer treatment [11,12]. However, it is critical to track and monitor changes of genes and cells during the treatment. Molecular imaging has emerged as an technology that effectively track and monitor genes and cells during treatment [13,14].