Inhibition of beclin1 affects the chemotherapeutic sensitivity of osteosarcoma.
This study was conducted to explore the role of autophagy in cisplatin-resistant osteosarcoma. Cisplatin-resistant osteosarcoma cell line (MG63/DDP) was obtained from parental MG63 by treating cisplatin with an intermittent stepwise selection protocol. The autophagy in MG63/DDP and MG63 was fully analyzed by immunofluorescence and western blot analysis. Meanwhile, the autophagy and the sensitivity to cisplatin for MG63/DDP and MG63 after inhibition of beclin1 were analyzed in vitro and in vivo. Increased autophagy was observed in cisplatin resistant MG63/DDP cells and in the cisplatin-treated MG63 and MG63/DDP cells. Meanwhile, inhibition the beclin1 significantly inhibited the formation of autophagosome and resulted in the increase in the sensitivity to cisplatin for both MG63 and MG63/DDP cells in vitro and in vivo. In conclusion, autophagy is implicated in the cisplatin resistant osteosarcoma, and inhibition of beclin1 could be a target for improving osteosarcoma therapy.
Department of Osteology, Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
Wenxin
W
Wu
Department of Otoalryngology-Head Neck Surgery, Third Xiangya Hospital, Central South University Changsha, Hunan, China.
Wei
W
Li
Department of Osteology, Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
Yong
Y
Zhou
Department of Osteology, Third Xiangya Hospital, Central South University Changsha 410013, Hunan, China.
Chaoyue
C
Zhang
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D021881:DNA, Catalytic / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D021881:DNA, Catalytic; D008565:Membrane Proteins; D002945:Cisplatin
Cisplatin; MG63; autophagy; beclin1; osteosarcoma