Abstract
Objective Studies have unveiled that the components of Tripterygium wilfordii Hook F (TWHF) such as celastrol could attenuate apoptosis and proliferation of various tumor cells. This study is focused on the radiosensitization effect and apoptotic pathways of celastrol via the inhibition of the c-myc gene and the influence of which combined with radiotherapy on the proliferation, apoptosis, invasion, and metastasis of chondrosarcoma cells. Methods A variety of bioinformatic tools were applied to explore the expression level and prognosis of the c-myc gene in different tumor cells and chondrosarcoma cells. We used pharmacology network to analyze the components, pathways, targets, molecular functions of TWHF and explore the relevant effective components over the MYC gene. Clone formation assay, CCK-8 assay, flow cytometry, and transwell migration assay were applied to detect the effects of celastrol on the expression of c-myc gene, cell apoptosis, and cell cycle. Radiation therapy was used to observe the radiosensitization effect of celastrol on chondrosarcoma. Results This study shows that the c-myc gene is overexpressed in various tumor cells and bone tumor cells to varying degrees. Celastrol can significantly inhibit the expression of the c-myc gene, induce G2/M phase arrest through regulation of G2/M phase-related proteins, and promote SW1353 cell apoptosis through the mitochondrial signaling pathway. In addition, we also found that the use of triptorubin to inhibit c-myc gene expression in combination with radiotherapy can increase the osteosarcoma cells' apoptosis rate through the mitochondrial signaling pathway significantly. Conclusions Our study validated the radiosensitization effect of celastrol through knocking down the expression of the c-myc gene to induce G2/M phase arrest and provides a new idea for the treatment of refractory or recurrent chondrosarcoma that is not sensitive to radiotherapy.
Highlights
Chondrosarcoma is a highly malignant tumor characterized by the production of the cartilage matrix by tumor cells, which is the second most commonly malignant bone tumor, with an incidence of 1 in 1,000,000 people [1, 2]
The result confirms that the combination therapy promotes the apoptosis of chondrosarcoma, which is attributed to the radiosensitization effect of celastrol by downregulating the expression of c-myc and inducing the G2/M phase arrest and the induction of chondrosarcoma apoptosis through the mitochondrial signaling pathway
Accumulating evidence indicates that cell cycle G2/M phase arrest is one of the key factors to enhance the sensitivity of radiotherapy [15, 28, 29]
Summary
Studies have unveiled that the components of Tripterygium wilfordii Hook F (TWHF) such as celastrol could attenuate apoptosis and proliferation of various tumor cells. This study is focused on the radiosensitization effect and apoptotic pathways of celastrol via the inhibition of the c-myc gene and the influence of which combined with radiotherapy on the proliferation, apoptosis, invasion, and metastasis of chondrosarcoma cells. Celastrol can significantly inhibit the expression of the c-myc gene, induce G2/M phase arrest through regulation of G2/M phase-related proteins, and promote SW1353 cell apoptosis through the mitochondrial signaling pathway. We found that the use of triptorubin to inhibit c-myc gene expression in combination with radiotherapy can increase the osteosarcoma cells’ apoptosis rate through the mitochondrial signaling pathway significantly. Our study validated the radiosensitization effect of celastrol through knocking down the expression of the c-myc gene to induce G2/M phase arrest and provides a new idea for the treatment of refractory or recurrent chondrosarcoma that is not sensitive to radiotherapy
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