DOX-Vit D, a Novel Doxorubicin Delivery Approach, Inhibits Human Osteosarcoma Cell Proliferation by Inducing Apoptosis While Inhibiting Akt and mTOR Signaling Pathways.

摘要: Doxorubicin (DOX) is a very potent and effective anticancer agent. However, the effectiveness of DOX in osteosarcoma usually limited by acquired drug resistance. Recently, Vitamin D (Vit-D) was shown to suppress growth many human cancer cells. Taken together, we synthesized DOX-Vit conjugating Vit-D order increase delivery into cells mitigate chemoresistance associated with DOX. For this purpose, MG63 were treated 10 µM or for 24 h. Thereafter, MTT, real-time PCR western blot analysis used determine cell proliferation, genes proteins expression, respectively. Our results showed that D, but not DOX, significantly elicited an apoptotic signal as evidenced induction death receptor, Caspase-3 BCLxs genes. Mechanistically, D-induced apoptogens credited activation p-JNK p-p38 signaling pathway inhibition proliferative proteins, p-Akt p-mTOR. findings propose suppressed inducing apoptosis while inhibiting survival pathways. may serve novel approach potentiate