CXCR4 knockdown enhances sensitivity of paclitaxel via the PI3K/Akt/mTOR pathway in ovarian carcinoma

被引：0

作者：

Zi, Dan ^{[1
,2
,3
,4
,5
,6
]}

Li, Qing ^{[7
,8
,10
]}

Xu, Cheng-xiong ^{[7
,8
,10
]}

Zhou, Zhi-Wei ^{[9
]}

Song, Guan-Bin ^{[9
]}

Hu, Cheng-Bin ^{[11
]}

Wen, Fang ^{[2
]}

Yang, Han-Lin ^{[2
]}

Nie, Lei ^{[2
]}

Zhao, Xing ^{[3
]}

Tan, Jun ^{[4
,5
]}

Zhou, Shu-Feng ^{[6
,12
]}

He, Zhi-Xu ^{[3
,13
]}

机构：

[1] Guizhou Prov Peoples Hosp, Dept Obstet & Gynecol, Guiyang 550002, Guizhou, Peoples R China

[2] Guizhou Med Univ, Dept Obstet & Gynecol, Affiliated Hosp, Guiyang 550004, Peoples R China

[3] Guizhou Med Univ, Guizhou Med Univ, Key Lab Adult Stem Cell Transformat Res, Stem Cell & Tissue Engn Res Ctr, Guiyang 550004, Peoples R China

[4] Guizhou Med Univ, Key Lab Endem & Ethn Dis, Minist Educ, Key Lab Mol Biol, Guiyang 550004, Peoples R China

[5] Guizhou Med Univ, Key Lab Mol Biol, Minist Educ, Guiyang 550004, Peoples R China

[6] Univ S Florida, Dept Pharmaceut Sci, Coll Pharm, Tampa, FL 33612 USA

[7] Third Mil Med Univ, Daping Hosp, Ctr Canc, Chongqing 40042, Peoples R China

[8] Third Mil Med Univ, Res Inst Surg, Ctr Canc, Chongqing 40042, Peoples R China

[9] Univ Texas SouthWestern Med Ctr, Dept Radiat Oncol, Dallas, TX 75390 USA

[10] Chongqing Univ, Coll Bioengn, Key Lab Biorheol Sci & Technol, Minist Educ, Chongqing 400030, Peoples R China

[11] Univ S Florida, Dept Comp Sci & Engn, Tampa, FL 33620 USA

[12] Huaqiao Univ, Coll Chem Engn, Dept Bioengn & Biotechnol, Xiamen 361021, Fujian, Peoples R China

[13] Zunyi Med Univ, Dept Pediat, Affiliated Hosp, Zunyi 563000, Guizhou, Peoples R China

来源：

AGING-US | 2022年 / 14卷 / 11期

基金：

中国国家自然科学基金;

关键词：

CXCR4; PI3K/Akt/mTOR; CSCs; ovarian cancer; PTX; EPITHELIAL-MESENCHYMAL TRANSITION; CELL INVASION; CANCER; METASTASIS; OVEREXPRESSION; ACTIVATION; RECEPTORS; PROMOTES; LUNG; AXIS;

D O I：

暂无

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy. EOC control remains difficult, and EOC patients show poor prognosis regarding metastasis and chemotherapy resistance. The aim of this study was to estimate the effect of CXCR4 knockdown-mediated reduction of cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) stemness and enhancement of chemotherapy sensitivity in EOC. Mechanisms contributing to these effects were also explored. Our data showed distinct contribution of CXCR4 overexpression by dependent PI3K/Akt/mTOR signaling pathway in EOC development. CXCR4 knockdown resulted in a reduction in CSCs and EMT formation and enhancement of chemotherapy sensitivity in tumor cells, which was further advanced by blocking CXCR4-PI3K/Akt/mTOR signaling. This study also documented the critical role of silencing CXCR4 in sensitizing ovarian CSCs to chemotherapy. Thus, targeting CXCR4 to suppress EOC progression, specifically in combination with paclitaxel (PTX) treatment, may have clinical application value.

引用

页码：4673 / 4698

页数：26

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