Development of a real-time imaging system for hypoxic cell apoptosis

Go Kagiya, Ryohei Ogawa, Fuminori Hyodo, Kei Yamashita, Mizuki Nakamura, Ayumi Ishii, Yukihiko Sejimo, Shintaro Tominaga, Masaharu Murata, Yoshikazu Tanaka, Masanori Hatashita

    Research output: Contribution to journalArticlepeer-review

    1 Citation (Scopus)

    Abstract

    Hypoxic regions within the tumor form due to imbalances between cell proliferation and angiogenesis; specifically, temporary closure or a reduced flow due to abnormal vasculature. They create environments where cancer cells acquire resistance to therapies. Therefore, the development of therapeutic approaches targeting the hypoxic cells is one of the most crucial challenges for cancer regression. Screening potential candidates for effective diagnostic modalities even under a hypoxic environment would be an important first step. In this study, we describe the development of a real-time imaging system to monitor hypoxic cell apoptosis for such screening. The imaging system is composed of a cyclic luciferase (luc) gene under the control of an improved hypoxic-responsive promoter. The cyclic luc gene product works as a caspase-3 (cas-3) monitor as it gains luc activity in response to cas-3 activation. The promoter composed of six hypoxic responsible elements and the CMV IE1 core promoter drives the effective expression of the cyclic luc gene in hypoxic conditions, enhancing hypoxic cell apoptosis visualization. We also confirmed real-time imaging of hypoxic cell apoptosis in the spheroid, which shares properties with the tumor. Thus, this constructed system could be a powerful tool for the development of effective anticancer diagnostic modalities.

    Original languageEnglish
    Pages (from-to)16009
    Number of pages1
    JournalMolecular Therapy - Methods and Clinical Development
    Volume3
    DOIs
    Publication statusPublished - Mar 16 2016

    All Science Journal Classification (ASJC) codes

    • Molecular Medicine
    • Molecular Biology
    • Genetics

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