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01.12.2011 | Original Paper

Slug inhibition upregulates radiation-induced PUMA activity leading to apoptosis in cholangiocarcinomas

verfasst von: Kejun Zhang, Bingyuan Zhang, Yun Lu, Chuandong Sun, Wei Zhao, Xuelong Jiao, Jilin Hu, Peng Mu, Hai Lu, Changyong Zhou

Erschienen in: Medical Oncology | Sonderheft 1/2011

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Abstract

Resistance of cholangiocarcinoma to irradiation therapy is a major problem in cancer treatment. Slug, a snail family transcription factor, is a suppressor of PUMA (p53 upregulated modulator of apoptosis), which has been shown to be involved in the control of apoptosis. In this study, we investigated whether the modulation of Slug expression, using adeno-associated-virus-mediated transfer of siRNA targeting Slug gene (rAAV2-Slug siRNA), affects cholangiocarcinoma sensitivity to radiation. In the present study, we used rAAV2-Slug siRNA to downregulate the expression of Slug in QBC939 cholangiocarcinoma cell lines in vitro before γ-irradiation. In vivo studies were done with orthotopic cholangiocarcinoma, and radiosensitivity was evaluated both in vitro and in vivo. rAAV2-Slug siRNA transfection resulted in downregulation of the levels of Slug in QBC939 cells. In addition, rAAV2-Slug siRNA, in combination with radiation, increased levels of the PUMA, which contributes to the radiosensitivity of cholangiocarcinomas. Finally, treatment with rAAV2-Slug siRNA plus γ-irradiation completely regressed tumor growth in orthotopic cholangiocarcinomas model. In summary, integrating gene therapy with radiotherapy could have a synergistic effect, thereby improving the survival of patients with cholangiocarcinomas.

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Titel: Slug inhibition upregulates radiation-induced PUMA activity leading to apoptosis in cholangiocarcinomas
verfasst von: Kejun Zhang
Bingyuan Zhang
Yun Lu
Chuandong Sun
Wei Zhao
Xuelong Jiao
Jilin Hu
Peng Mu
Hai Lu
Changyong Zhou
Publikationsdatum: 01.12.2011
Verlag: Springer US
Erschienen in: Medical Oncology / Ausgabe Sonderheft 1/2011
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI: https://doi.org/10.1007/s12032-010-9759-x

Springer Medizin

Slug inhibition upregulates radiation-induced PUMA activity leading to apoptosis in cholangiocarcinomas

Abstract

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