Inhibitory activity of acteoside in melanoma via regulation of the ERβ-Ras/Raf1-STAT3 pathway,Archives of Biochemistry and Biophysics

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Inhibitory activity of acteoside in melanoma via regulation of the ERβ-Ras/Raf1-STAT3 pathway
Archives of Biochemistry and Biophysics ( IF 3.8 ) Pub Date : 2021-06-23 , DOI: 10.1016/j.abb.2021.108978
Yuanyuan Wu ₁ , Mengnan Zeng ₁ , Ruiqi Xu ₁ , Beibei Zhang ₁ , Shengchao Wang ₁ , Benke Li ₁ , Yuxuan Kan ₁ , Bing Cao ₁ , Xiaoke Zheng ₁ , Weisheng Feng ₁

Affiliation

Background

Melanoma is an aggressive cancer with a rapidly increasing incidence rate worldwide. Acteoside has been shown to have antitumor effects in multiple human cancers; however, the underlying function and mechanisms of acteoside in melanoma remain unclear.

Purpose

This study explored the inhibitory effect of acteoside on melanoma and the possible mechanisms.

Methods

Acteoside (15 mg/kg, 30 mg/kg) was administered to mice daily for 21 days. ICI182,780 (0.5 mg/kg) was intraperitoneally injected 30 min before acteoside administration three times a week to evaluate whether the effects elicited by acteoside were mediated via the estrogen receptor. Tumor growth and metabolism, cardiac function, ROS and apoptosis levels in the spleen, serum inflammatory factors, and immune cells in the spleen were monitored. STAT3, p-STAT3, CD31, and survivin levels in tumor tissues were measured via immunofluorescence. Ras, Raf1, STAT3, p-STAT3, Bcl-2, Bax, cleaved caspase-3, and cleaved caspase-9 levels in tumor tissues were determined via Western Blotting.

Results

The results showed that acteoside inhibited melanoma growth, alleviated inflammation levels in mice, attenuated ROS and apoptosis levels in the spleen, downregulated the levels of CD31, survivin, Ras, Raf1, p-STAT3, and Bcl-2, and upregulated the levels of ERβ, Bax, cleaved caspase-3, and cleaved caspase-9. Moreover, the effect of acteoside was blocked by ICI182,780.

Conclusion

Acteoside may promote the apoptosis of tumor cells by regulating the ERβ-Ras/Raf1-STAT3 signaling axis, thus inhibiting the occurrence and development of melanoma.

中文翻译：

通过调节 ERβ-Ras/Raf1-STAT3 通路抑制黑素瘤中的梨果苷活性

背景

黑色素瘤是一种侵袭性癌症，在全球范围内的发病率迅速增加。Acteoside 已被证明对多种人类癌症具有抗肿瘤作用；然而，苦杏仁苷在黑色素瘤中的潜在功能和机制仍不清楚。

目的

本研究探讨了猕猴桃苷对黑色素瘤的抑制作用及其可能的机制。

方法

每天向小鼠施用 Acteoside (15 mg/kg, 30 mg/kg)，持续 21 天。ICI182,780 (0.5 mg/kg) 每周 3 次在给予乙酰胆碱前 30 分钟腹膜内注射，以评估由乙酰胆碱引起的作用是否是通过雌激素受体介导的。监测脾脏中的肿瘤生长和代谢、心脏功能、ROS和细胞凋亡水平、血清炎症因子和脾脏中的免疫细胞。通过免疫荧光检测肿瘤组织中的 STAT3、p-STAT3、CD31 和存活蛋白水平。通过蛋白质印迹法测定肿瘤组织中的 Ras、Raf1、STAT3、p-STAT3、Bcl-2、Bax、cleaved caspase-3 和 cleaved caspase-9 水平。

结果

结果表明，猕猴桃抑制黑色素瘤的生长，减轻小鼠的炎症水平，减弱脾脏的 ROS 和细胞凋亡水平，下调 CD31、存活蛋白、Ras、Raf1、p-STAT3 和 Bcl-2 的水平，并上调ER β、Bax、裂解的 caspase-3 和裂解的 caspase-9。此外，ICI182,780 阻断了梨果苷的作用。