Nie Juan, Yang Hong-Mei, Sun Chao-Yue, Liu Yan-Lu, Zhuo Jian-Yi, Zhang Zhen-Biao, Lai Xiao-Ping, Su Zi-Ren, Li Yu-Cui
Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China.
Guangdong Province Traditional Chinese Medical Hospital, Guangzhou, China.
Front Pharmacol. 2018 Jun 14;9:615. doi: 10.3389/fphar.2018.00615. eCollection 2018.
Bleomycin (BLM) is a broad spectrum anti-tumor drug and 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 (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 and experiments. experiments showed that BLM combined with SCU in the treatment of mice bearing H22 ascites tumor prolonged the survival time, alleviated BLM-induced pulmonary fibrosis, reduced the production of TNF-α; IL-6, and the levels of MDA and MPO. BLM combined with SCU increased the apoptotic rate of H22 ascites cells and the levels of cleaved-caspases-3 and -8. Furthermore, BLM combined with SCU increased the protein expression of p53 and gene expression of miR-29b, and decreased the expression of TGF-β1. experiment results showed that BLM combined with SCU inhibited the viability of H22 cells and MRC-5 cells, 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, indicating SCU as a potential adjuvant for BLM in the future.
博来霉素(BLM)是一种广谱抗肿瘤药物,可诱发肺纤维化。作为一种无免疫抑制作用的抗肿瘤药物,迫切需要找到一种能减轻BLM副作用的药物。灯盏花素(SCU)是从灯盏细辛(Vant.)Hand-Mazz中提取的一种黄酮,具有抗炎活性以及抑制肿瘤细胞生长、迁移和侵袭的能力。然而,SCU与BLM联合治疗在肿瘤中的作用尚不清楚。本研究旨在通过体内和体外实验探究BLM联合SCU治疗肿瘤的可能效果及相关机制。体内实验表明,BLM联合SCU治疗荷H22腹水瘤小鼠可延长生存时间,减轻BLM诱导的肺纤维化,降低肿瘤坏死因子-α、白细胞介素-6的产生以及丙二醛和髓过氧化物酶的水平。BLM联合SCU可提高H22腹水细胞的凋亡率以及半胱天冬酶-3和-8的裂解水平。此外,BLM联合SCU可增加p53蛋白表达和miR-29b基因表达,并降低转化生长因子-β1的表达。体外实验结果表明,BLM联合SCU可抑制H22细胞和MRC-5细胞的活力,促进H22细胞凋亡,上调p53蛋白表达,并下调MRC-5细胞中α-平滑肌肌动蛋白和I型胶原蛋白的蛋白表达。这些实验结果表明,SCU可增强BLM的抗肿瘤作用并减轻BLM诱导的肺纤维化,表明SCU未来可能成为BLM的潜在佐剂。