Knockdown of CDK6 enhances glioma sensitivity to chemotherapy

Li,Bing; He,Hua; Tao,Bang-Bao; Zhao,Zhen-Yu; Hu,Guo-Han; Luo,Chun; Chen,Ju-Xiang; Ding,Xue-Hua; Sheng,Ping; Dong,Yan; Zhang,Ling; Lu,Yi-Cheng

doi:10.3892/or.2012.1884

Knockdown of CDK6 enhances glioma sensitivity to chemotherapy

Authors:
- Bing Li
- Hua He
- Bang-Bao Tao
- Zhen-Yu Zhao
- Guo-Han Hu
- Chun Luo
- Ju-Xiang Chen
- Xue-Hua Ding
- Ping Sheng
- Yan Dong
- Ling Zhang
- Yi-Cheng Lu
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Affiliations: Department of Neurosurgery, Changzheng Hospital, Second Affiliated Hospital of Second Military Medical University, Shanghai 200003, P.R. China, Department of Neurosurgery, Changzheng Hospital, Second Affiliated Hospital of Second Military Medical University, Shanghai 200003, P.R. China, Department of Neurosurgery, the 105th Hospital of PLA, Hefei, Anhui 230000, P.R. China, Editorial Department, Chinese Journal of Neuromedicine, Zhujiang Hospital, Guangzhou, Guangdong 510282, P.R. China
Published online on: June 25, 2012 https://doi.org/10.3892/or.2012.1884
Pages: 909-914

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Abstract

Chemotherapy is widely used for the treatment of glioma. Given the high resistance of brain neoplasm tissues to chemotherapy, it is important to find new methods to improve the effects of chemotherapy. However, the molecular mechanisms underlying glioma resistance to chemotherapy are largely unknown. Here, we demonstrate that CDK6, a cell cycle regulator, is significantly upregulated in glioma cells, and the increasing expression of CDK6 correlates well with the grades of glioma malignancy. Using shRNA-mediated CDK6 knockdown, we found that the proliferation and survival of tumor cells were dramatically inhibited. Moreover, CDK6 knockdown in the U251 glioma cell line caused significant increase in the apoptosis of U251 cells treated with temozolomide (TMZ). Furthermore, CDK6 knockdown reduced the expression level of drug resistance genes such as MRP and MDR. These data indicate that CDK6 is an important mediator of glioma resistance to chemotherapy. Our findings provide a new strategy for the development of chemotherapy sensitizer.

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