Yang Xinyue, Lu Yang, Kuang Qin, Wu Yong, Tan Xin, Lan Jizhong, Qiang Zhe, Feng Tao
Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China.
College of Pharmacy, Chongqing Medical University, Chongqing, China.
Front Oncol. 2023 May 29;13:1164250. doi: 10.3389/fonc.2023.1164250. eCollection 2023.
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) and , 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. 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.
前列腺癌是目前男性中最常见的恶性肿瘤。鉴于当前传统抗癌疗法的局限性，迫切需要新的高风险治疗方法。先前的研究表明，胚胎干细胞（ESCs）可以逆转肿瘤细胞的致瘤表型。然而，直接将人类胚胎干细胞（hESCs）用于癌症治疗仍存在挑战。为了促进hESCs的实际应用，我们建立了一个由前列腺癌细胞系和hESCs组成的共培养系统，并研究了共培养系统上清液（Co-Sp）的抗肿瘤活性及其潜在机制。Co-Sp以浓度依赖的方式降低了前列腺癌细胞的活力，显著抑制了集落形成，并诱导细胞周期停滞在G0/G1期。此外，Co-Sp促进了前列腺癌细胞的凋亡，并抑制了细胞迁移和侵袭。研究还表明，Co-Sp在异种移植模型中抑制了肿瘤生长。机制研究表明，Co-Sp降低了前列腺癌细胞中细胞周期蛋白D1、细胞周期蛋白E、细胞周期蛋白依赖性激酶4（CDK4）、细胞周期蛋白依赖性激酶2（CDK2）、基质金属蛋白酶9（MMP-9）、基质金属蛋白酶1（MMP-1）和Bcl-2的表达，并增加了p21、裂解的半胱天冬酶-9、裂解的半胱天冬酶-3、裂解的聚（ADP-核糖）聚合酶（PARP）和Bax的表达。此外，Co-Sp降低了细胞和肿瘤组织中PI3K、AKT和mTOR的磷酸化。综上所述，我们的结果表明Co-Sp具有强大的抗肿瘤活性，可直接抑制肿瘤生长。我们的发现为hESCs在癌症治疗中的应用提供了一种新的有效方法，并为临床干细胞治疗贡献了一种新策略。
