Ligustrazine reverts anthracycline chemotherapy resistance of human breast cancer by inhibiting JAK2/STAT3 signaling and decreasing fibrinogen gamma chain (FGG) expression

被引：9
作者：
Liu, Yu-Lin [1 ]
Yan, Ze-Xuan [2 ,3 ]
Xia, Yu [1 ]
Xie, Xiao-Ye [4 ]
Zhou, Kai [2 ,3 ]
Xu, Li-Li [1 ]
Shi, Yan-Long [4 ]
Wang, Qiang [1 ,4 ]
Bi, Jing-Wang [4 ]
机构：
[1] Navy 971 Hosp PLA, Clin Lab, Qingdao 266071, Shandong, Peoples R China
[2] Army Med Univ, Inst Pathol, Southwest Hosp, Chongqing 400038, Peoples R China
[3] Army Med Univ, Southwest Canc Ctr, Southwest Hosp, Chongqing 400038, Peoples R China
[4] 960 Hosp PLA, Dept Oncol, 25 Shifan Rd, Jinan 250031, Shandong, Peoples R China
来源：
AMERICAN JOURNAL OF CANCER RESEARCH | 2020年 / 10卷 / 03期
基金：
中国国家自然科学基金;
关键词：
Ligustrazine; fibrinogen gamma chain; breast cancer; JAK2/STAT3; pathway; anthracycline; chemotherapy resistance; ACID-DERIVATIVES; GROWTH-FACTORS; TETRAMETHYLPYRAZINE; PROMOTES; CELLS; METASTASIS; EPIRUBICIN; ACTIVATION; APOPTOSIS; DESIGN;
D O I：
暂无
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Chemotherapy resistance is a major challenge for breast cancer treatment. It is necessary to elucidate the mechanisms of anthracycline resistance to develop new chemosensitizers for breast cancer. In this study, we explored the effects of ligustrazine (TMP) on reverting anthracycline resistance of breast cancer cells, as well as its related mechanisms. Clinical significance of fibrinogen gamma chain (FGG) expression was also analyzed in breast cancer tissues. We provided evidence that breast tumor cell derived FGG participated in anthracycline chemoresistance of breast cancer. Further, TMP reverted epirubicin resistance by inhibiting JAK2/STAT3 signaling and decreasing FGG expression. Meanwhile, the elimination of cancer stem cell was observed in TMP treated chemoresistant breast cancer cells. Clinical analysis demonstrated that patients with FGG expressing breast cancer showed a dramatically low response to anthracycline-based chemotherapy and poor survival. Our data collectively indicated that FGG was an independent detrimental factor for anthracycline based chemotherapy for breast cancer patients. TMP was a novel chemosensitizer for FGG-induced anthracycline chemoresistance in breast cancer treatment.
引用
收藏
页码：939 / +
页数：15
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