Integrated using UMI-77 and Curcumin Synergistic Treating Osteosarcoma by Targeting a Cuproptosis-Related Prognostic Model
Author:
Fu Zhaoyu1, Wang Nan1, Ren Jia1, Kong Yuanhang1, Yang Jihao1, Su Gao1, Yang Guohui1
Affiliation:
1. Department of Emergency Surgery, the First Affiliated Hospital of Zhengzhou University
Abstract
Abstract
Background
Among malignant bone sarcomas, osteosarcoma (OS) is the most frequent among young people. In recent studies, cuproptosis has been shown to play an important role in tumor progression. Evidence demonstrates that the combinatorial treatment with traditional Chinese medicine and western medicine improves the therapeutic effect on cancer, including OS. However, the combinatorial treatment targeting cuproptosis for OS remains elusive.
Materials and Methods
LASSO regression analysis was employed to establish and evaluate a cuproptosis-related prognostic model. The CIBERSORT algorithm was performed to demonstrate the significant differences in immune cell infiltration between low- and high-risk groups. Next, the CellMiner database was used to obtain potential drugs which target the risk score-related genes. Finally, we performed the network pharmacology and molecular docking studies to explore the combination of Chinese and western medicine on treatment of osteosarcoma.
Results
We found that the Chinese medicine, curcumin, and the western medicine, UMI-77 synergistic treating OS both in vivo and vitro. LASSO regression analysis was employed to establish and evaluate a cuproptosis-related prognostic model. Moreover, the CIBERSORT algorithm was performed to demonstrate the significant differences in immune cell infiltration between low- and high-risk groups. Notably, prognostic genes were related to 106 drugs obtained from the CellMiner database. Network pharmacology and molecular docking studies demonstrated that curcumin, the main active ingredient of curcumaelongae Rhizoma, targeted the suppressor gene, CLTC.
Conclusion
Our findings demonstrated that the combination of curcumin and UMI possess certain effect on osteosarcoma. And this study provides a theoretical framework for the integration of traditional Chinese medicine with western medicine for treating OS.
Publisher
Research Square Platform LLC
Reference46 articles.
1. A. H. VON MIKECZ, P. H. H., H.-H, PETER & U. KRAWINKEL 1995. Autoantigenic epitopes on eukaryotic L7. Clin Exp Immunol;, 100:205–213. 2. Antitumor activity of curcumin is mediated through the induction of apoptosis in AK-5 tumor cells;KHAR A;FEBS Lett.,1999 3. A novel small-molecule inhibitor of mcl-1 blocks pancreatic cancer growth in vitro and in vivo;ABULWERDI F;Mol Cancer Ther,2014 4. Biological activities of curcumin and its analogues (Congeners) made by man and Mother Nature;ANAND P;Biochem Pharmacol,2008 5. Ottaviania, M. A., EL-BABA, C., ELNAGGAR, M. H., ELKHOLY, Y. O., MOTTAWEA, M., JOHAR, D., AL SHEHABI, T. S., KOBEISSY, F., MOUSSALEM, C., MASSAAD, E., OMEIS, I., DARWICHE, N. & EID, A. H. 2020. Novel therapeutic strategies for spinal osteosarcomas. Semin Cancer Biol, 64, 83–92.
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