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rAAV-delivered PTEN therapeutics for prostate cancer.

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机构： [1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 88 South Keyuan Road, Chengdu 610041, China. [2]Horae Gene Therapy Center, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA.

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Effective treatments for prostate cancer (PCa) require further development, and previous studies have reported that PTEN and its downstream target CDKN1B are significantly downregulated in PCa cells compared with normal cells. Therefore, modulation of PTEN and CDKN1B expression might be a promising therapeutic approach for PCa treatment. Expression of PTEN and CDKN1B was verified in specimens from PCa patients and transgenic adenocarcinoma mouse prostate (TRAMP) mice. The effect of PTEN on PCa cell migration, apoptosis, and the cell cycle was analyzed in vitro using a wound-healing assay and flow cytometry. We assessed the ability of intraprostatic and intratumoral injections of recombinant adeno-associated virus (rAAV) 9 expressing Pten or Cdkn1b into TRAMP mice and a subcutaneous tumor xenograft mouse model, respectively, to inhibit PCa progression. PTEN and CDKN1B were significantly downregulated in human and mouse PCa samples, and CDKN1B expression correlated positively with PTEN expression. PTEN overexpression significantly inhibited cell migration and cell-cycle progression and promoted apoptosis in PCa cells by decreasing Ccnd1 expression and increasing that of Cdkn1b. Importantly, treatment with the rAAV9.Pten or rAAV9.Cdkn1b extended the lifespan of TRAMP mice and inhibited the growth rate of tumor xenografts by regulating downstream gene expression. Moreover, neoplasia in treated prostates was significantly diminished compared with that in control prostates, and apoptosis was markedly observed in xenografts treated with Pten or Cdkn1b. These data indicate that rAAV-based PTEN/CDKN1B delivery is promising for the development of novel therapeutics for PCa.© 2021 The Authors.

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出版当年[2022]版：

大类 | 1 区

医学

小类 | 1 区医学：研究与实验

最新[2023]版：

大类 | 2 区

医学

小类 | 2 区医学：研究与实验

第一作者：

第一作者机构： [1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 88 South Keyuan Road, Chengdu 610041, China. [2]Horae Gene Therapy Center, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. [*1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 88 South Keyuan Road, Chengdu 610041, China

通讯作者：

通讯机构： [1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 88 South Keyuan Road, Chengdu 610041, China. [2]Horae Gene Therapy Center, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA. [*1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 88 South Keyuan Road, Chengdu 610041, China [*2]Horae Gene Therapy Center, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605, USA

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