Combination of anginex gene therapy and radiation decelerates the growth and pulmonary metastasis of human osteosarcoma xenografts

Abstract

Investigate whether rAAV‐anginex gene therapy combined with radiotherapy could decrease growth and pulmonary metastasis of osteosarcoma in mice and examine the mechanisms involved in this therapeutic strategy. During in vitro experiment, multiple treatment regimes (rAAV‐eGFP, radiotherapy, rAAV‐anginex, combination therapy) were applied to determine effects on proliferation of endothelial cells (ECs) and G‐292 osteosarcoma cells. During in vivo analysis, the same multiple treatment regimes were applied to osteosarcoma tumor‐bearing mice. Use microcomputed tomography to evaluate tumor size. Eight weeks after tumor cell inoculation, immunohistochemistry was used to assess the therapeutic efficacy according to microvessel density (MVD), proliferating cell nuclear antigen (PCNA), and terminal‐deoxynucleotidyl transferase‐mediated nick‐end labeling (TUNEL) assays. Metastasis of lungs was also evaluated by measuring number of metastatic nodules and wet weight of metastases. The proliferation of ECs and the tumor volumes in combination therapy group were inhibited more effectively than the other three groups at end point (P < 0.05). Cell clone assay showed anginex had radiosensitization effect on ECs. Immunohistochemistry showed tumors from mice treated with combination therapy exhibited the lowest MVD and proliferation rate, with highest apoptosis rate, as confirmed by IHC staining for CD34 and PCNA and TUNEL assays (P < 0.05). Combination therapy also induced the fewest metastatic nodules and lowest wet weights of the lungs (P < 0.05). rAAV‐anginex combined with radiotherapy induced apoptosis of osteosarcoma cells and inhibited tumor growth and pulmonary metastasis on the experimental osteosarcoma models. We conclude that the primary mechanism of this process may be due to sensitizing effect of anginex to radiotherapy.

DEPDC1 as a crucial factor in the progression of human osteosarcoma

“…For this study, we adopted a subcutaneous osteosarcoma mouse model. 26,27 Although an in situ mouse experimental proximal bone model has also been broadly used for osteosarcoma research, [28][29][30][31] the subcutaneous tumor model has the advantage of establishing the direct observation of the tumor growth and being able to readily collect important data such as animal weight, tumor growth curve, and tumor weight. At the same time, a subcutaneous tumor can be used for correlation analysis of tissue and body fluid samples, which is widely used in biomedical research and drug development.…”

Preparation and identification of anti-breast cancer cells peptides released from yak milk casein

“…These agents are promising and safe anti-cancer drugs (4). For example, Anginex, an artificial peptide targeting the anti-angiogenic proteins, is capable of inhibiting metastasis of osteosarcoma (5). Besides synthetic peptides, there are many anti-cancer peptides released from various foods such as rice bran (6), soybean (7), common bean (8), and bovine milk (9).…”

Hsa_circ_0097271 Knockdown Attenuates Osteosarcoma Progression via Regulating miR-640/MCAM Pathway

“…Accordingly, 5-year survival rates have increased from no more than 30% to more than 70% [ 4 , 5 ]. As molecular pathogenesis continues to advance, gene therapy has become a controllable, targeted, and specific treatment for OS [ 6 ]. Therefore, novel oncogenic factors should be identified to further provide treatment strategies for OS.…”