Knockdown of CDK6 enhances glioma sensitivity to chemotherapy.
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.
Department of Neurosurgery, Changzheng Hospital, Second Affiliated Hospital of Second Military Medical University, Shanghai 200003, PR China.
Bing
B
Li
Hua
H
He
Bang-Bao
BB
Tao
Zhen-Yu
ZY
Zhao
Guo-Han
GH
Hu
Chun
C
Luo
Ju-Xiang
JX
Chen
Xue-Hua
XH
Ding
Ping
P
Sheng
Yan
Y
Dong
Ling
L
Zhang
Yi-Cheng
YC
Lu
D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001254:Astrocytoma / Q000188:drug therapy* / Q000201:enzymology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics* / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D034622:RNA Interference; D000077204:Temozolomide; D014158:Transcription, Genetic
D018906:Antineoplastic Agents, Alkylating; C452880:Atp5md protein, rat; D008565:Membrane Proteins; D003606:Dacarbazine; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6; D000077204:Temozolomide