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山奈酚通过调节 Ki67 表达抑制雄激素依赖性和非依赖性前列腺癌。

Kaempferol suppresses androgen-dependent and androgen-independent prostate cancer by regulating Ki67 expression.

机构信息

Guangxi Zhuang Yao Medicine Center of Engineering and Technology, Guangxi University of Chinese Medicine, Nanning, 530200, China.

School of Foreign Languages, Nanning Normal University, Nanning, 530299, China.

出版信息

Mol Biol Rep. 2022 Jun;49(6):4607-4617. doi: 10.1007/s11033-022-07307-2. Epub 2022 Mar 14.

Abstract

PURPOSE

Kaempferol is a natural flavonoid that has been reported to be active against many cancers, including prostate cancer, breast cancer and colon cancer. In our previous study, we found kaempferol could act as a selective androgen receptor modulator, thereby suppress development of benign prostatic hyperplasia. This finding inspired us to further explore the effect and the mechanism of action of kaempferol on prostate cancer.

METHODS

Plate clone formation assay was performed to detect the effect of kaempferol on cell proliferation. Flow cytometry was used to detect the impact of kaempferol on cell apoptosis and cell cycle distribution. qPCR, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to detect the expression of gene and protein of Ki67 which is a biomarker of cell proliferation.

RESULTS

In the present study, we found kaempferol could dramatically suppress androgen-dependent and androgen-independent prostate cancer cells proliferation and induce their apoptosis. Furthermore, we found that kaempferol induced cell cycle to be arrested at G1 phase in 22Rv1 cells but at S and G2 phase in PC-3 cells. In addition, we detected the mRNA and protein of Ki67 which is corresponding to the cell proliferation and found that kaempferol could significantly inhibit Ki67 expression at mRNA level but increase its expression at protein levels in both androgen-dependent and androgen-independent prostate cancer cells.

CONCLUSION

Taken together, kaempferol inhibited the proliferation of androgen-dependent and androgen-independent prostate cancer cells by regulating the expression of Ki67. These findings further shed light on the mechanism of action of kaempferol on anti-prostate cancer.

摘要

目的

山柰酚是一种天然类黄酮,据报道对许多癌症具有活性,包括前列腺癌、乳腺癌和结肠癌。在我们之前的研究中,我们发现山柰酚可以作为一种选择性雄激素受体调节剂,从而抑制良性前列腺增生的发展。这一发现促使我们进一步探索山柰酚对前列腺癌的作用和作用机制。

方法

采用平板克隆形成实验检测山柰酚对细胞增殖的影响。流式细胞术检测山柰酚对细胞凋亡和细胞周期分布的影响。qPCR、免疫荧光染色和酶联免疫吸附试验检测增殖标志物 Ki67 的基因和蛋白表达。

结果

本研究发现山柰酚可显著抑制雄激素依赖性和雄激素非依赖性前列腺癌细胞增殖并诱导其凋亡。此外,我们发现山柰酚诱导 22Rv1 细胞的细胞周期停滞在 G1 期,而在 PC-3 细胞中停滞在 S 和 G2 期。此外,我们检测了与细胞增殖相对应的 Ki67 的 mRNA 和蛋白,发现山柰酚可显著抑制雄激素依赖性和雄激素非依赖性前列腺癌细胞中 Ki67 的 mRNA 表达,但可增加其蛋白表达。

结论

综上所述,山柰酚通过调节 Ki67 的表达抑制雄激素依赖性和雄激素非依赖性前列腺癌细胞的增殖。这些发现进一步阐明了山柰酚抗前列腺癌的作用机制。

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