Human embryonic stem cells exert antitumor effects on prostate cancer cells in a co-culture microenvironment

作者全名："Yang, Xinyue; Lu, Yang; Kuang, Qin; Wu, Yong; Tan, Xin; Lan, Jizhong; Qiang, Zhe; Feng, Tao"

作者地址："[Yang, Xinyue; Lu, Yang; Kuang, Qin; Wu, Yong; Tan, Xin; Lan, Jizhong; Qiang, Zhe; Feng, Tao] Chongqing Med Univ, Key Lab Biochem & Mol Pharmacol Chongqing, Chongqing, Peoples R China; [Yang, Xinyue; Lu, Yang; Kuang, Qin; Wu, Yong; Tan, Xin; Lan, Jizhong; Feng, Tao] Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China; [Qiang, Zhe] Chongqing Acad Chinese Mat Med, Inst Pharmacol Toxicol, Chongqing, Peoples R China"

通信作者："Qiang, Z; Feng, T (通讯作者)，Chongqing Med Univ, Key Lab Biochem & Mol Pharmacol Chongqing, Chongqing, Peoples R China.; Feng, T (通讯作者)，Chongqing Med Univ, Coll Pharm, Chongqing, Peoples R China.; Qiang, Z (通讯作者)，Chongqing Acad Chinese Mat Med, Inst Pharmacol Toxicol, Chongqing, Peoples R China."

来源：FRONTIERS IN ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001002528700001

JCR分区：Q2

影响因子：3.5

年份：2023

卷号：13

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：human embryonic stem cells; prostate cancer; co-culture; antitumor effects; PI3K; Akt; mTOR pathway

摘要："Prostate cancer is currently the most common malignancy among men. Given the limitations of current conventional anticancer therapies, new high-risk treatments are urgently needed. Previous studies have shown that embryonic stem cells (ESCs) can reverse the tumorigenic phenotype of tumor cells. However, there are still challenges in using human ESCs (hESCs) directly in cancer treatment. To facilitate the practical application of hESCs, we established a co-culture system consisting of prostate cancer cell lines and hESCs and investigated the antitumor activity of the supernatant of the co-culture system (Co-Sp) in vitro and in vivo, as well as the underlying mechanisms involved. The Co-Sp decreased the viability of prostate cancer cells in a concentration-dependent manner, significantly inhibited colony formation, and induced cell cycle arrest at the G0/G1 phase of the cell cycle. In addition, Co-Sp promoted apoptosis of prostate cancer cells and inhibited cell migration and invasion. In vivo studies also revealed that Co-Sp inhibited tumor growth in the xenograft model. Mechanistic studies showed that Co-Sp reduced the expression of cyclin D1, cyclin E, CDK4, CDK2, MMP-9, MMP-1, and Bcl-2, and increased the expression of p21, cleaved caspase-9, cleaved caspase-3, cleaved PARP, and Bax in prostate cancer cells. Furthermore, the Co-Sp decreased the phosphorylation of PI3K, AKT, and mTOR in cells and tumor tissues. Taken together, our results indicated that the Co-Sp has potent antitumor activity and could directly inhibit tumor growth. Our findings provide a new and effective way for the application of hESCs in cancer therapy and contribute to a new strategy for clinical stem cell therapy."

基金机构：National Natural Science Foundation of China [82002712]; Chongqing graduate research innovation project [CYS21238]; Chongqing Natural Science Foundation [cstc2021jcyj-msxmX0793]

基金资助正文："Funding The work was supported by the National Natural Science Foundation of China (No. 82002712), the Chongqing graduate research innovation project (grant number CYS21238), and the Chongqing Natural Science Foundation (No. cstc2021jcyj-msxmX0793)."