Expression of Beclin1 in osteosarcoma and the effects of down-regulation of autophagy on the chemotherapeutic sensitivity.
To explore the expression of Beclin1 in osteosarcoma and investigate the effects of down-regulation of autophagy on the chemotherapeutic sensitivity to cisplatin (DDP), the expression of Beclin1 in 28 specimens of osteosarcoma (group A) and 19 specimens of normal bone tissues (group B) were immunohistochemically detected. The expression of Beclin1 mRNA in MG63 cells treated with different concentrations of DDP was examined with RT-PCR. After down-regulation of autophagy in MG63 cells by an autophagy inhibitor, 3-methyladenine (3-MA), the cell proliferation inhibition rate of MG63 cells treated with DDP was evaluated by using the MTT assay. The positive rates of Beclin1 were 67.85% in group A and 94.73% in group B. Its expression was lower in osteosarcoma than in normal bone tissues, with a significant difference found between them (P<0.05). RT-PCR showed that the expression of Beclin1 mRNA in the cells treated with high-dose DDP were higher than that in the non-treated cells, and no significant difference in the expression of Beclin1 mRNA was found between the cells treated with low-dose DDP and the non-treated cells. There was a positive correlation between the level of Beclin1 mRNA expression and the concentration of DDP. MTT assay showed that the proliferation inhibition rates of the cell treated with 3-MA and DDP combined were substantially increased when compared with those treated with DDP alone (P<0.01). This study demonstrated that autophagy may be implicated in the carcinogenesis of osteosarcoma, and DDP may induce autophagy in the MG63 cells. It also suggests that the down-regulated autophagy could increase chemotherapeutic sensitivity of DDP to osteosarcoma.
Zhang
Zhicai
Z
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. pingfang00@yahoo.com.cn
Shao
Zengwu
Z
Xiong
Liming
L
Che
Biao
B
Deng
Chao
C
Xu
Weiwei
W
D000970:Antineoplastic Agents / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy; D000071186:Beclin-1; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D012333:RNA, Messenger; D002945:Cisplatin