کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8296796 | 1536770 | 2015 | 19 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Liposomal short-chain C6 ceramide induces potent anti-osteosarcoma activity in vitro and in vivo
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موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
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چکیده انگلیسی
Osteosarcoma (OS) remains one deadly disease for many affected patients. The search for novel and more efficient anti-OS agents is urgent. In the current study, we demonstrated that liposome-packed C6 ceramide exerted potent cytotoxic effect against established (U2OS and MG-63 lines) and primary human OS cells. Meanwhile, the liposomal C6 (ceramide) induced caspase-mediated apoptotic death in OS cells. Liposomal C6 was significantly more potent than conventional free C6 in inhibiting OS cells, yet it was safe to non-cancerous bone cells (primary murine osteoblasts or human MLO-Y4 osteocytic cells). At the signaling level, we showed that liposomal C6 potently inhibited Akt activation in OS cells. Further studies revealed that a low dose of liposomal C6 dramatically sensitized the in vitro anti-OS activity of two conventional chemodrugs: methotrexate (MTX) and doxorubicin. In vivo, intravenous injection of liposomal C6 inhibited Akt activation and suppressed U2OS xenograft growth in nude mice without causing apparent toxicities. Meanwhile, when given at a low-dose (5 mg/kg body weight), liposomal C6 dramatically sensitized MTX's anti-U2OS activity in vivo. Collectively, our data demonstrate that liposomal C6 exerts potent anti-tumor activity in preclinical OS models.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 468, Issues 1â2, 4â11 December 2015, Pages 274-280
Journal: Biochemical and Biophysical Research Communications - Volume 468, Issues 1â2, 4â11 December 2015, Pages 274-280
نویسندگان
Lei Zhai, Nan Sun, Zhe Han, Hai-chao Jin, Bo Zhang,