Inhibition of autophagy and enhancement of endoplasmic reticulum stress increase sensitivity of osteosarcoma Saos-2 cells to cannabinoid receptor agonist WIN55,212-2.
WIN55,212-2, a cannabinoid receptor agonist, can activate cannabinoid receptors, which has proven anti-tumour effects in several tumour types. Studies showed that WIN can inhibit tumour cell proliferation and induce apoptosis in diverse cancers. However, the role and mechanism of WIN in osteosarcoma are still unclear. In this study, we examined the effect of WIN55,212-2 on osteosarcoma cell line Saos-2 in terms of cell viability and apoptosis. Meanwhile, we further explored the role of endoplasmic reticulum stress and autophagy in apoptosis induced by WIN55,212-2. Our results showed that the cell proliferation of Saos-2 was inhibited by WIN55,212-2 in a dose-dependent and time-dependent manner. WIN55,212-2-induced Saos-2 apoptosis through mitochondrial apoptosis pathway. Meanwhile, WIN55,212-2 can induce endoplasmic reticulum stress and autophagy in Saos-2 cells. Inhibition of autophagy and enhancement of endoplasmic reticulum stress increased apoptosis induced by WIN55,212-2 in Saos-2 cells. These findings indicated that WIN55,212-2 in combination with autophagic inhibitor or endoplasmic reticulum stress activator may shed new light on osteosarcoma treatment. Copyright © 2016 John Wiley & Sons, Ltd.
Department of Orthopedic Surgery, Qi Lu Hospital, Shandong University, Shandong, China.|Department of Orthopedic Surgery, Yantai Shan Hospital, Shandong, China.
Guodong
G
Zhang
Department of Orthopedic Surgery, Yantai Shan Hospital, Shandong, China.
Haiyong
H
Bi
Department of Urology, China-Japan Union Hospital, Jilin, China.
Ji
J
Gao
Department of Orthopedic Surgery, Yantai Shan Hospital, Shandong, China.
Xing
X
Lu
Department of Orthopedic Surgery, Qi Lu Hospital, Shandong University, Shandong, China.
Yanping
Y
Zheng
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D048588:Benzoxazines / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002738:Chloroquine / Q000494:pharmacology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology*; D009281:Naphthalenes / Q000494:pharmacology*; D012516:Osteosarcoma / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D048588:Benzoxazines; D063386:Cannabinoid Receptor Agonists; D009025:Morpholines; D009281:Naphthalenes; C025946:3-methyladenine; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D002738:Chloroquine; D000225:Adenine
WIN55,212-2; autophagy; endoplasmic reticulum stress; osteosarcoma