Nanoscale bubble delivered YCD-TK/Cx26 gene therapeutic system suppresses tumor growth by inducing necrosis of tumor tissues in mouse Xenograft bladder cancer models

摘要

OBJECTIVE: Bladder cancer is considered as the fifth most common cancer in the whole world. This study aimed to investigate the anti-tumor effects of Nanoscale bubbles delivered yeast cytosine deaminase thymidine kinase/connexin 26 (YCD-TK/Cx26) on tumor cell proliferation and tumor growth. MATERIALS AND METHODS: Nanoscale bubble was prepared using thin-film hydration-sonication method. Nanoscale bubble-LV5-YCD-TK+PCD-Cx26 was generated and transfected into BIU-87 cells. MTT assay was employed to detect cell viability. Apoptosis was determined using a flow cytometry assay. YCD-TK and Cx26 expressions were detected using Western blot and Real Time-PCR (RT-PCR). BIU-87 cells were transplanted into mice to establish Xenograft models. The tumor volume was recorded. HE staining was used to examine necrosis areas in tumor tissues. RESULTS: Nanoscale bubble (Nanoscale bubble-LV5-YCD-TK+PCD-Cx26) successfully mediated YCD-TK and Cx26 gene expression in BIU-87 cells. Nanoscale bubble delivered YCD-TK/Cx26 expression significantly inhibited cell viability and induced apoptosis compared to Nanoscale bubble-LV5-YCD-TK and Nanoscale bubble group (p0.05). Nanoscale bubble delivered YCD-TK/Cx26 expression triggered significantly higher levels of bystander effect compared to single YCD-TK or single Cx26 gene (p0.05). Nanoscale bubble delivered YCD-TK/Cx26 expression significantly reduced tumor volume in mouse Xenograft bladder cancer model compared to LV5-YCD-TK and 5-FC+GCV group (p0.05). Nanoscale bubble delivered YCD-TK/Cx26 expression significantly reduced the necrosis of tumor tissues in mouse Xenograft bladder cancer model compared to LV5-YCD-TK group and 5-FC+GCV group (p0.05). CONCLUSIONS: Nanoscale bubble delivered YCD-TK/Cx26 gene therapeutic system efficiently reduced BIU-87 cell proliferation in vitro, and suppressed tumor growth by inducing necrosis of tumor tissues in mouse Xenograft bladder cancer models.