亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整的填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

TrxR1 to promote adriamycin resistance in MCF-7 breast cancer cells by upregulating both gene expression level and enzyme activity: Reversed by shikonin.

MCF-7型 癌细胞 阿霉素 细胞凋亡 细胞毒性 癌症研究 内质网 膜联蛋白 转染 多重耐药 乳腺癌化疗 药理学 癌症 医学 乳腺癌 细胞培养 化学 抗药性 生物 体外 生物化学 化疗 内科学 微生物学 人体乳房 遗传学
作者
Jinqing Yang,Jinhai Tang
出处
期刊:Journal of Clinical Oncology [American Society of Clinical Oncology]
卷期号:39 (15_suppl): e15070-e15070
标识
DOI:10.1200/jco.2021.39.15_suppl.e15070
摘要

e15070 Background: Adriamycin is one of the effective drugs commonly used in the treatment of advanced breast cancer, but its high incidence of drug resistance and cardiotoxicity limit the application of doxorubicin. Recent evidence shows that increased antioxidant capacity of cancer cells is associated with resistance to chemotherapy. Shikonin, a derivative of Lithospermum erythrorhizon Sieb.et Zucc, displays broad antitumor activity and direct cytotoxicity on various tumor cells. Our previous study shows that shikonin was enabled to directly binding and inhibiting TrxR1, which significantly downregulates intracellular ROS in cancer cells, suggesting that shikonin might be a promising drug candidate. In this study, we identified the relationship between TrxR1 and chemotherapeutic drug resistance in cancer cells and effects of shikonin with and without adriamycin on adriamycin-resistance cells. Methods: The direct DTNB reduction assay was employed to test the enzyme activity of TrxR1. Cultured ADR-resistant MCF-7 cells were assayed for their half maximal inhibitory concentration (IC50) values and apoptosis using an CCK8 assay and Annexin V-FITC/PI-labeled flow cytometry. Drug resistance was evaluated by inhibitory concentration (IC50) values and immunoblotting multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP). TrxR1 knockdown was silenced by siRNA, leading to reducing the IC50 value of ADR-resistant MCF-7 cells. Dysfunctional endoplasmic reticulum was measured by western blot analysis of endoplasmic reticulum (ER) stress signaling pathways and observation of morphology using a transmission electron microscope. Results: We found that the TrxR1 was significantly enhanced in adriamycin-resistant (ADR/MCF7) cells.Furthermore, the decreased TrxR1 function by TrxR1-knockdown or TrxR1 inhibitor piperlongumine increased MCF-7 cells sensitivity to adriamycin. Treatment of ADR/MCF7 cells with shikonin (2.5,5,10,20,40 μM) dose-dependently inhibited TrxR1 enzyme activity and the clearance of dysfunctional endoplasmic reticulum, and induced cell apoptosis. Conclusions: Our results suggest that TrxR1 is critical for adriamycin resistance in breast cancer cells(ADR/MCF7),and shikonin or other inhibitors of TrxR1 would be potential in the treatment of cancer cells with adriamycin resistance.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
见鹰完成签到,获得积分10
40秒前
见鹰发布了新的文献求助20
45秒前
1分钟前
汉堡包应助liubo采纳,获得10
1分钟前
科目三应助Original采纳,获得10
1分钟前
1分钟前
风中小刺猬完成签到,获得积分10
1分钟前
Owen应助cindy采纳,获得10
1分钟前
Original发布了新的文献求助10
1分钟前
largpark完成签到 ,获得积分10
1分钟前
1分钟前
1分钟前
cindy发布了新的文献求助10
1分钟前
liubo发布了新的文献求助10
1分钟前
Original完成签到,获得积分10
1分钟前
cindy完成签到,获得积分10
2分钟前
爆米花应助科研通管家采纳,获得10
3分钟前
CATH完成签到 ,获得积分10
3分钟前
雨天爱吃冰淇淋完成签到 ,获得积分10
3分钟前
3分钟前
金钰贝儿完成签到,获得积分10
4分钟前
qujinzhi完成签到 ,获得积分10
4分钟前
Ava应助李小猫采纳,获得10
4分钟前
李小猫完成签到,获得积分10
4分钟前
4分钟前
李小猫发布了新的文献求助10
5分钟前
奋斗的杰发布了新的文献求助10
6分钟前
ang完成签到,获得积分10
6分钟前
7分钟前
隐形曼青应助奋斗的杰采纳,获得10
7分钟前
8分钟前
8分钟前
wrl2023发布了新的文献求助10
8分钟前
9分钟前
奋斗的杰发布了新的文献求助10
10分钟前
辣椒完成签到 ,获得积分10
10分钟前
10分钟前
10分钟前
123关闭了123文献求助
11分钟前
丘比特应助救救小王叭采纳,获得10
11分钟前
高分求助中
Evolution 10000
ISSN 2159-8274 EISSN 2159-8290 1000
Becoming: An Introduction to Jung's Concept of Individuation 600
Ore genesis in the Zambian Copperbelt with particular reference to the northern sector of the Chambishi basin 500
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
A new species of Velataspis (Hemiptera Coccoidea Diaspididae) from tea in Assam 500
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3162323
求助须知:如何正确求助?哪些是违规求助? 2813330
关于积分的说明 7899698
捐赠科研通 2472818
什么是DOI,文献DOI怎么找? 1316528
科研通“疑难数据库(出版商)”最低求助积分说明 631365
版权声明 602142