Scutellarin Enhances Antitumor Effects and Attenuates the Toxicity of Bleomycin in H22 Ascites Tumor-Bearing Mice.

Published on Jun 14, 2018in Frontiers in Pharmacology5.811
· DOI :10.3389/FPHAR.2018.00615
Juan Nie6
Estimated H-index: 6
(Guangzhou University of Chinese Medicine),
Hongmei Yang9
Estimated H-index: 9
(Guangzhou University of Chinese Medicine)
+ 6 AuthorsYu-Cui Li21
Estimated H-index: 21
(Guangzhou University of Chinese Medicine)
Sources
Abstract
Bleomycin (BLM), a broad spectrum anti-tumor drug, have side effects of inducing pulmonary fibrosis. As an anti-tumor drug without immunosuppression, it is urgent to find a drug that reduces the side effects of BLM. Scutellarin (SCU), a flavone extracted from Erigeron breviscapus (Vant.) Hand-Mazz, has anti-inflammatory activity and ability to inhibit tumor cell growth, migration and invasion. However, the combined role of SCU and BLM treatment in tumor is unclear. This study aimed to investigate the possible effect and related mechanisms of BLM combined with SCU in the treatment of tumor through in vivo and in vitro experiments. In vivo experiments showed that BLM combined with SCU in the treatment of H22 ascites tumor-bearing mice prolonged the survival time, alleviated BLM-induced pulmonary fibrosis, reduced the production of TNF-α, and IL-6, the activities of MDA and MPO. BLM combined with SCU increased the apoptotic rate of H22 ascites cells and the activities of caspases-3 and -8. Furthermore, BLM combined with SCU increased the protein expression of p53 and gene expression of miR-29b, decreased the expression of TGF-β1. In vitro experiment results showed that BLM combined with SCU inhibited the H22 cells and MRC-5 cells proliferation, promoted H22 cell apoptosis, up-regulated the protein expression of p53 and down-regulated the protein expression of α-SMA and Collagen-I in MRC-5 cells. These experimental results suggested that SCU could enhance the anti-tumor effect of BLM and reduce BLM-induced pulmonary fibrosis side effects, indicating SCU as a potential adjuvant for BLM clinically in the future.
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References63
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Source
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