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

Abstract：

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 (p<0.05). Nanoscale bubble delivered YCD-TK/Cx26 expression triggered significantly higher levels of bystander effect compared to single YCD-TK or single Cx26 gene (p<0.05). 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 (p<0.05). 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 (p<0.05). 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.

journal_name

Eur Rev Med Pharmacol Sci

journal_title

European review for medical and pharmacological sciences

authors

Fu YR,Luo Y,Xie X,Lu W,Zhang R,Xiong B,Chen F

doi

10.26355/eurrev_201909_18839

subject

Has Abstract

pub_date

2019-09-01 00:00:00

pages

7338-7349

issue

17

eissn

1128-3602

issn

2284-0729

journal_volume

23

pub_type

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