首页|青蒿素通过TIGIT/CD155信号轴调控4T1乳腺癌细胞转移与凋亡

青蒿素通过TIGIT/CD155信号轴调控4T1乳腺癌细胞转移与凋亡

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乳腺癌是严重影响女性生命健康的恶性肿瘤之一.近年来,中药植物活性成分-青蒿素(ar-temisinin,ART)的抗肿瘤作用愈显突出.然而,目前仍不清楚ART 在治疗乳腺癌转移方面的效果及其作用机制.本文以小鼠乳腺癌细胞4T1 及小鼠乳腺上皮细胞HC11 为研究对象,探索ART 抑制4T1 细胞转移并诱导凋亡的作用,并揭示其可能的分子机制.MTS(CellTiter 96 ®AQueous One Solution Cell Proliferation Assay,MTS)实验表明,ART 能够明显抑制4T1 细胞活力,且具有ART 浓度及处理时长依赖性.通过细胞集落形成、Transwell 及细胞划痕结果分析发现,ART 能够显著抑制乳腺癌4T1 细胞转移.流式细胞术结果显示,ART 能够促进肿瘤细胞的ROS 产生、线粒体膜电位丧失、细胞周期阻滞进而引起细胞凋亡.生物信息分析方法及研究证实,TIGIT 极显著高表达(P<0.001)与乳腺癌转移密切相关,ART 能够显著降低TIGIT/CD155 信号轴的基因表达水平(P<0.001,P<0.01).综上所述,本研究初步揭示了ART 可能通过阻断TIGIT/CD155 信号轴抑制乳腺癌转移的调控机制,为ART 作为乳腺癌的潜在治疗药物提供依据,有助于探索利用中药有效成分治疗肿瘤的新途径.
Artemisinin Regulates 4T1 Breast Cancer Cell Migration and Apoptosis Through the TIGIT/CD155 Signaling Axis
Breast cancer is one of the malignant tumors that seriously affects women's lives and health.In recent years,the anti-tumor effect of artemisinin(ART),an active ingredient of traditional Chinese medicine,has become more prominent.However,the effectiveness of ART in the treatment of breast cancer metastasis and its mechanism are still unclear.In this paper,we used the mouse breast cancer cell 4T1 and mouse mammary epithelial cell HC11 to explore the role of ART in inhibiting metastasis and inducing apoptosis.The MTS assay showed that ART was able to significantly inhibit the viability of 4T1 cells in a concentration and time-dependent manner.Analysis of cell colony formation,Transwell and cell scratch results revealed that ART significantly inhibited the metastasis of breast cancer 4T1 cells.Flow cytometry results showed that ART promoted ROS production,loss of mitochondrial membrane potential,cell cycle arrest and thus apoptosis in tumor cells.Bioinformatic analysis methods and studies confirmed that extremely significant high expression of TIGIT(P<0.001)was closely associated with breast cancer metastasis,and that ART was able to significantly reduce the gene expression level of the TIGIT/CD155 signaling axis(P<0.001,P<0.01).In summary,this study reveals the regulatory mechanism by which ART may inhibit breast cancer metastasis by blocking the TIGIT/CD155 signaling axis,which pro-vides a basis for ART as a potential therapeutic agent for breast cancer,and contributes to the exploration of a new way of treating tumors using the active ingredients of Chinese herbal medicine.

artemisininbreast cancer metastasisapoptosisTIGIT-CD155 signal axis

冯亚婵、张皓杰、杜朝、郭学玲、王英泽

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河北科技大学食品与生物学院细胞工程研究室,石家庄 050018

青蒿素 乳腺癌转移 细胞凋亡 TIGIT-CD155信号轴

国家自然科学基金河北省自然科学基金河北省自然科学基金河北科技大学研究生创新能力培养项目河北科技大学博士科研基金

81760750H2020208018C2020208023XJCXZZSS20230781760750

2024

中国生物化学与分子生物学报
中国生物化学与分子生物学会 北京大学

中国生物化学与分子生物学报

CSTPCD北大核心
影响因子:0.617
ISSN:1007-7626
年,卷(期):2024.40(1)
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