The regulation of proliferation and apoptosis in hepatocellular carcinoma via insulin-like growth factor 1 receptor.

OBJECTIVES: Insulin-like growth factor 1 receptor (IGF-1R) is a transmembrane tyrosine kinase receptor of the insulin receptor family. Its expression is consistently increased in hepatocellular carcinoma (HCC) tissue, and it participates in hepatic carcinogenesis. Targeting IGF-1R may be a potential therapeutic approach against hepatocellular carcinoma. This study therefore aimed to explore the effect of IGF-1R on hepatocellular carcinoma cells. METHODS: IGF-1R silencing cell lines were established by small-interfering RNAs in hepatocellular carcinoma cell line SMMC7721, after which the proliferation, invasion, and apoptosis of SMMC7721 was evaluated. The activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and the expression of bone morphogenetic protein (BMP)-2 and BMP-7 were measured using Western blot analysis. RESULTS: The results indicated that the knockdown of IGF-1R can inhibit the proliferation and invasion of HCC and promote the apoptosis of SMMC7721 by inhibiting the PI3K/AKT signaling pathway. Furthermore, depletion of IGF-1R was found to suppress the expression of BMP-2 and BMP-7. CONCLUSIONS: The findings suggest that IGF-1R plays an important role in the progression of HCC. Therefore, IGF-1R is a potential target for the treatment of HCC in clinic.

Tumor cell membrane-camouflaged responsive nanoparticles enable MRI-guided immuno-chemodynamic therapy of orthotopic osteosarcoma.

Osteosarcoma is a refractory bone disease in young people that needs the updating and development of effective treatment. Although nanotechnology is widely applied in cancer therapy, poor targeting and inadequate efficiency hinder its development. In this study, we prepared alendronate (ALD)/K7M2 cell membranes-coated hollow manganese dioxide (HMnO2) nanoparticles as a nanocarrier to load Ginsenoside Rh2 (Rh2) for Magnetic Resonance imaging (MRI)-guided immuno-chemodynamic combination osteosarcoma therapy. Subsequently, the ALD and K7M2 cell membranes were successively modified on the surface of HMnO2 and loaded with Rh2. The tumor microenvironment (TME)-activated Rh2@HMnO2-AM nanoparticles have good bone tumor-targeting and tumor-homing capabilities, excellent GSH-sensitive drug release profile and MRI capability, and attractive immuno-chemodynamic combined therapeutic efficiency. The Rh2@HMnO2-AM nanoparticles can effectively trigger immunogenic cell death (ICD), activate CD4+/CD8+ T cells in vivo, and upregulate BAX, BCL-2 and Caspase-3 in cellular level. Further results revealed that Rh2@HMnO2-AM enhanced the secretion of IL-6, IFN-γ and TNF-α in serum and inhibited the generation of FOXP3+ T cells (Tregs) in tumors. Moreover, the Rh2@HMnO2-AM treatment significant restricted tumor growth in-situ tumor-bearing mice. Therefore, Rh2@HMnO2-AM may serve as an effective and bio-friendly nanoparticle platform combined with immunotherapy and chemodynamic therapy to provide a novel approach to osteosarcoma therapy.