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从水果中分离得到的澳洲茄碱具有很强的抗胰腺癌活性。

Solasodine, Isolated from Fruits, Has a Potent Anti-Tumor Activity Against Pancreatic Cancer.

机构信息

Medical Laboratory, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, 200438, People's Republic of China.

出版信息

Drug Des Devel Ther. 2021 Apr 13;15:1509-1519. doi: 10.2147/DDDT.S266746. eCollection 2021.

Abstract

BACKGROUND

Increasing evidences have revealed that solasodine, isolated from fruits, has multiple functions such as anti-oxidant, anti-tumor and anti-infection. However, its role in pancreatic cancer has not been well studied.

METHODS

To explore the role of solasodine in pancreatic cancer, human pancreatic cell lines including SW1990 and PANC1 were treated with different concentrations of solasodine for 48 h, and cell viability was evaluated by MTT assay, cell invasion and migration were evaluated by Transwell assay. The effect of solasodine on the apoptosis of SW1990 and PANC1 cells was detected by flow cytometry. To further explore the antitumor effect of solasodine in vivo, an SW1990 tumor-bearing mouse model was constructed. The effects of solasodine on cytokines in the serum of SW1990 tumor-bearing mice were also evaluated by ELISA assay.

RESULTS

Specifically, in vitro, solasodine could significantly inhibit the proliferation of pancreatic cancer cell lines SW1990 and PANC1 cells. Flow cytometric analysis indicated that solasodine could induce apoptosis of SW1990 and PANC1 cells. Western blot assay indicated that solasodine could significantly inhibit the activation of Cox-2/Akt/GSK3β signal pathway. Meanwhile, the release of Cytochrome c from mitochondria to cytoplasm which can raise the caspases cascade (C-caspase 3 and C-caspase 9) was significantly enhanced by solasodine. In vivo, the results showed that solasodine had potent anti-tumor activities with a lower cytotoxicity. In addition, the serum TNF-α, IL-2 and IFN-γ levels in SW1990 tumor-bearing mice after the treatment of solasodine was significantly increased.

CONCLUSION

Taken together, our results suggested that the solasodine could prevent the progression of pancreatic cancer by inhibiting proliferation and promoting apoptosis, as well as stimulating immunity, suggesting that solasodine might be a potential therapeutic strategy for pancreatic cancer.

摘要

背景

越来越多的证据表明,茄碱从水果中分离出来,具有多种功能,如抗氧化、抗肿瘤和抗感染。然而,它在胰腺癌中的作用尚未得到很好的研究。

方法

为了探讨茄碱在胰腺癌中的作用,用不同浓度的茄碱处理人胰腺细胞系 SW1990 和 PANC1 48 小时,用 MTT 法评估细胞活力,用 Transwell 法评估细胞侵袭和迁移。用流式细胞术检测茄碱对 SW1990 和 PANC1 细胞凋亡的影响。为了进一步探讨茄碱在体内的抗肿瘤作用,构建了 SW1990 荷瘤小鼠模型。用 ELISA 法检测茄碱对 SW1990 荷瘤小鼠血清中细胞因子的影响。

结果

具体来说,在体外,茄碱能显著抑制胰腺癌细胞系 SW1990 和 PANC1 细胞的增殖。流式细胞术分析表明,茄碱能诱导 SW1990 和 PANC1 细胞凋亡。Western blot 分析表明,茄碱能显著抑制 Cox-2/Akt/GSK3β 信号通路的激活。同时,线粒体中细胞色素 c 向细胞质的释放明显增强,从而引发 caspase 级联反应(C-caspase 3 和 C-caspase 9)。体内结果表明,茄碱具有较强的抗肿瘤活性,细胞毒性较低。此外,用茄碱治疗后,SW1990 荷瘤小鼠血清中 TNF-α、IL-2 和 IFN-γ 水平明显升高。

结论

综上所述,我们的研究结果表明,茄碱通过抑制增殖、促进凋亡以及刺激免疫来预防胰腺癌的进展,提示茄碱可能是治疗胰腺癌的一种潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/514d/8054575/e862243edb77/DDDT-15-1509-g0001.jpg

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