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p53 dry gene powder enhances anti-cancer effects of chemotherapy against malignant pleural mesothelioma

Gene Therapy volume 31, pages 119–127 (2024)Cite this article

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Abstract

Dry gene powder is a novel non-viral gene-delivery system, which is inhalable with high gene expression. Previously, we showed that the transfection of p16INK4a or TP53 by dry gene powder resulted in growth inhibitions of lung cancer and malignant pleural mesothelioma (MPM) in vitro and in vivo. Here, we report that dry gene powder containing p53- expression-plasmid DNA enhanced the therapeutic effects of cisplatin (CDDP) against MPM even in the presence of endogenous p53. Furthermore, our results indicated that the safe transfection with a higher plasmid DNA (pDNA) concentration suppressed MPM growth independently of chemotherapeutic agents. To develop a new therapeutic alternative for MPM patients without safety concerns over “vector doses”, our in vitro data provide basic understandings for dry gene powder.

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Fig. 1: The effects of p53-SFD in combination with CDDP or PEM on AB1 cell viability and cell cycle.
Fig. 2: The effect of lipofection or 2% p53-SFD on AB1 cell viability.
Fig. 3: The effect of different pDNA concentrations of p53-SFD under CDDP treatment on NCI-H2052 cell viability.
Fig. 4: The apoptosis of p53-SFD with CDDP in NCI-H2052.
Fig. 5: The cell cycle of p53-SFD with CDDP in NCI-H2052.
Fig. 6: Summary of the growth-inhibition mechanism of p53-SFD and CDDP in AB1 and NCI-H2052.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Randis Medical Developments Inc., Nagoya, Aichi, Japan

    Naomi Muramatsu

  2. Department of Drug Delivery Research, Faculty of Pharmacy, Meijo University, Nagoya, Aichi, Japan

    Naomi Muramatsu, Tomoyuki Okuda & Hirokazu Okamoto

  3. StateArt Inc., Chuo-ku, Tokyo, Japan

    Misa Ichikawa, Tomoko Katagiri, Yumi Taguchi & Takashi Hatanaka

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  1. Naomi Muramatsu
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  6. Tomoyuki Okuda
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  7. Hirokazu Okamoto
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Contributions

NM designed this study, collected the data, performed the analysis, and wrote the original draft. YT prepared the dry gene powder. YT, TK, MI, TO, and TH reviewed the manuscript. HO participated in the study design, revised the manuscript, and gave final approval of the version to be submitted. The work reported in the paper has been performed by the authors, unless clearly specified in the text. All authors contributed to the article and approved the submitted version.

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Correspondence to Hirokazu Okamoto.

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As this study does not involve animal studies, human subjects, human material, or human data, ethical approval is not applicable.

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Muramatsu, N., Ichikawa, M., Katagiri, T. et al. p53 dry gene powder enhances anti-cancer effects of chemotherapy against malignant pleural mesothelioma. Gene Ther 31, 119–127 (2024). https://doi.org/10.1038/s41434-023-00424-y

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