MicroRNA-326 sensitizes human glioblastoma cells to curcumin via the SHH/GLI1 signaling pathway.
Glioblastoma multiforme is the most malignant and common brain tumor in adults and is characterized by poor survival and high resistance to chemotherapy and radiotherapy. Among the new chemotherapy drugs, curcumin, a popular dietary supplement, has proven to have a potent anticancer effect on a variety of cancer cell types; however, it remains difficult to achieve a satisfactory therapeutic effect with curcumin using the traditional single-drug treatment. In this study, we found that expression of miR-326, a tumor suppressor microRNA in various tumor types, resulted in a marked increase of curcumin-induced cytotoxicity and apoptosis and a decrease of proliferation and migration in glioma cells. Moreover, we found that combination treatment of miR-326 and curcumin caused significant inhibition of the SHH/GLI1 pathway in glioma cells compared with either treatment alone, independent of p53 status. Furthermore, in vivo, the curcumin-induced increase in miR-326 expression altered the anti-glioma mechanism of this combination treatment, which further reduced tumor volume and prolonged the survival period compared to either treatment alone. Taken together, our data strongly support an important role for miR-326 in enhancing the chemosensitivity of glioma cells to curcumin.
a Department of Neurosurgery , The Second Affiliated Hospital of Harbin Medical University , Harbin , China.
Shi
S
Yin
a Department of Neurosurgery , The Second Affiliated Hospital of Harbin Medical University , Harbin , China.
Wenzhong
W
Du
a Department of Neurosurgery , The Second Affiliated Hospital of Harbin Medical University , Harbin , China.
Feng
F
Wang
a Department of Neurosurgery , The Second Affiliated Hospital of Harbin Medical University , Harbin , China.
Bo
B
Han
a Department of Neurosurgery , The Second Affiliated Hospital of Harbin Medical University , Harbin , China.
Yuqiong
Y
Cui
a Department of Neurosurgery , The Second Affiliated Hospital of Harbin Medical University , Harbin , China.
Dongbo
D
Yang
a Department of Neurosurgery , The Second Affiliated Hospital of Harbin Medical University , Harbin , China.
Hui
H
Chen
a Department of Neurosurgery , The Second Affiliated Hospital of Harbin Medical University , Harbin , China.
Daming
D
Liu
a Department of Neurosurgery , The Second Affiliated Hospital of Harbin Medical University , Harbin , China.
Xing
X
Liu
c Department of Neurosurgery , Daqing LongNan Hospital , Daqing , China.
Xiuwei
X
Zhai
a Department of Neurosurgery , The Second Affiliated Hospital of Harbin Medical University , Harbin , China.|b Neuroscience Institute, Heilongjiang Academy of Medical Sciences , Harbin , China.
Chuanlu
C
Jiang
D000328:Adult; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D000071676:Zinc Finger Protein GLI1 / Q000378:metabolism
D000970:Antineoplastic Agents; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C545322:MIRN326 microRNA, human; D035683:MicroRNAs; C509239:SHH protein, human; D000071676:Zinc Finger Protein GLI1; D003474:Curcumin
Curcumin; GLI1; MicroRNA; glioma; p53; tumor