Knockdown of CDK6 enhances glioma sensitivity to chemotherapy.

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.
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
Journal	Oncology reports (Oncol Rep) Vol. 28 Issue 3 Pg. 909-14 (Sep 2012) ISSN: 1791-2431 [Electronic] Greece
PMID	22736304 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antineoplastic Agents, Alkylating Atp5md protein, rat Membrane Proteins Dacarbazine PARP1 protein, human Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases CDK6 protein, human Cyclin-Dependent Kinase 6 Temozolomide
Topics	Animals Antineoplastic Agents, Alkylating (pharmacology) Astrocytoma (drug therapy, enzymology) Brain Neoplasms (drug therapy, enzymology) Cell Line, Tumor (drug effects) Cell Proliferation Cyclin-Dependent Kinase 6 (genetics, metabolism) Dacarbazine (analogs & derivatives, pharmacology) Drug Resistance, Neoplasm Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Knockdown Techniques Humans Membrane Proteins (metabolism) Mice Oligonucleotide Array Sequence Analysis Poly (ADP-Ribose) Polymerase-1 Poly(ADP-ribose) Polymerases (metabolism) RNA Interference Temozolomide Transcription, Genetic

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