苦参碱通过Akt/mTOR通路的保护性自噬在宫颈癌中发挥抗肿瘤活性。

Matrine exerts antitumor activity in cervical cancer by protective autophagy via the Akt/mTOR pathway and .

作者信息

Zhang Fan, Zhang Hua, Qian Wenjun, Xi Yuyan, Chang Lihua, Wu Xiaoling, Li Mu

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China.

Department of Clinical Medicine, Suzhou Vocational Health College, Suzhou, Jiangsu 215009, P.R. China.

出版信息

Oncol Lett. 2022 Apr;23(4):110. doi: 10.3892/ol.2022.13230. Epub 2022 Feb 7.

Abstract

Matrine is a quinazoline alkaloid extracted from . The aim of the present study was to determine whether matrine can induce autophagy in the human HeLa and SiHa cervical cancer cell lines and . Cell viability assay was used to assess the suppressive effect of matrine and cisplatin on the proliferation of HeLa and SiHa cells. A total of 28 4-week-old female BALB/c nude mice were used for the study. Autophagy and protein expression were observed via transmission electron microscopy, monodansylcadaverine and immunohistochemical staining and western blotting. The inhibitory effect of matrine on the proliferation of cervical cancer cells was time- and dose-dependent. The combination of matrine and cisplatin synergistically inhibited the proliferation of cervical cancer cells and . Transmission electron microscopy showed that after the addition of matrine, numerous autophagosomes and autophagolysosomes were observable in HeLa and SiHa cells, as demonstrated by monodansylcadaverine staining. Western blotting and immunohistochemical staining showed that as the concentration of matrine increased, the expression of the autophagy marker LC3A/B-II also increased significantly and . These findings suggested that matrine inhibited the proliferation of cervical cancer cells and induced autophagy by inhibiting the Akt/mTOR signaling pathway. Thus, matrine may represented a potential candidate in combination therapy for cervical cancer as an inducer of autophagy.

摘要

苦参碱是从……中提取的一种喹唑啉生物碱。本研究的目的是确定苦参碱是否能在人宫颈癌HeLa和SiHa细胞系中诱导自噬。采用细胞活力测定法评估苦参碱和顺铂对HeLa和SiHa细胞增殖的抑制作用。总共28只4周龄雌性BALB/c裸鼠用于该研究。通过透射电子显微镜、单丹磺酰尸胺以及免疫组织化学染色和蛋白质印迹法观察自噬和蛋白质表达情况。苦参碱对宫颈癌细胞增殖的抑制作用具有时间和剂量依赖性。苦参碱和顺铂联合使用可协同抑制宫颈癌细胞的增殖。透射电子显微镜显示,加入苦参碱后,在HeLa和SiHa细胞中可观察到大量自噬体和自噬溶酶体,单丹磺酰尸胺染色也证实了这一点。蛋白质印迹法和免疫组织化学染色显示,随着苦参碱浓度的增加,自噬标志物LC3A/B-II的表达也显著增加。这些发现表明,苦参碱通过抑制Akt/mTOR信号通路抑制宫颈癌细胞的增殖并诱导自噬。因此,苦参碱作为自噬诱导剂可能是宫颈癌联合治疗的潜在候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8318/8848215/0353ff5483d2/ol-23-04-13230-g00.jpg

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