Chk1 knockdown confers radiosensitization in prostate cancer stem cells | Zendy

Xiaobin Wang | Zendy; Zhikun Ma | Zendy; Zheng Xiao | Zendy; Hui Liu | Zendy; Zhongling Dou | Zendy; Xiaoshan Feng | Zendy; Haijun Shi | Zendy

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Chk1 knockdown confers radiosensitization in prostate cancer stem cells

Author(s) -

Xiaobin Wang,

Zhikun Ma,

Zheng Xiao,

Hui Liu,

Zhongling Dou,

Xiaoshan Feng,

Haijun Shi

Publication year - 2012

Publication title -

oncology reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.094

H-Index - 96

eISSN - 1791-2431

pISSN - 1021-335X

DOI - 10.3892/or.2012.2068

Subject(s) - radioresistance , cancer stem cell , cancer research , prostate cancer , cd44 , radiosensitivity , stem cell , biology , gene knockdown , cancer cell , cancer , cell cycle , dna damage , apoptosis , cell , medicine , microbiology and biotechnology , radiation therapy , cell culture , genetics , dna

Radioresistance is responsible for treatment failure after radiotherapyin localized prostate cancer, while prostate cancer stem cells promote radioresistanceby preferential activation of the DNA damage response. Chk1 inhibition has beenshown to sensitize many tumor cells to radiation. However, whether Chk1 inhibitioncan potentiate the cytotoxic effects of radiation on prostate cancer stem cellsremains to be elucidated. In this study, CD133+CD44+ cells were isolated usingmicrobeads and were found to possess cancer stem cell properties. Using shRNA,Chk1 was knocked down in the sorted CD133+CD44+ cells. Our results demonstratedthat Chk1 knockdown abrogated the radiation-induced G2/M arrest, inhibited DNAdamage repair and promoted premature mitosis, leading to increased apoptosis inthe radiated sorted CD133+CD44+ cells. Moreover, these effects were accompaniedby caspase-2 activation and the inactivation of phosphorylated Cdc25C and Cdc2.Our results suggest that Chk1 knockdown increases the radiosensitivity of CD133+CD44+prostate cancer stem cells. Chk1 knockdown in prostate cancer stem cells may bean effective therapeutic strategy against prostate cancer.

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