Feng Yigeng, Cao Hongwen, Zhao Wenyang, Chen Lei, Wang Dan, Gao Renjie
Surgical Department I (Urology Department), LONGHUA Hospital Shanghai University of Traditional Chinese Medicine, No. 725 Wanping Road South, Xuhui District, Shanghai 200032, China.
J Cancer. 2022 Nov 21;13(15):3652-3659. doi: 10.7150/jca.78246. eCollection 2022.
miR-143 is known to be downregulated in various cancer cells and tumors and generally plays a tumor-suppressor role. miR-143. However, the role of miR-143 in the mediation of the sensitivity of prostate cancer cells to abiraterone acetate remains unrevealed. The expression levels of miRNAs were determined by miRNA microarray and quantitative real-time PCR (qRT-PCR). The protein levels were assessed by Western blot assay. Cell viability and apoptosis were respectively measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. We identified that miR-143 was significantly downregulated in PC3-AbiR cells compared to PC3 cells. Overexpression of miR-143 promoted PC-AbiR sensitivity to abiraterone acetate in vitro and in vivo. We also revealed that miR-143 upregulation inhibited p-JNK (c-Jun N-terminal kinases) and increased p-Bcl2 (B-cell lymphoma 2), contributing to abiraterone acetate-induced apoptosis in PC3-AbiR cells. Finally, we showed that the combination of miR-143 and abiraterone acetate exerted the most profound tumor inhibition effect and prolonged the mice survival rate in PC3-AbiR tumor-bearing mice. Upregulation of miR-143 may serve as a new strategy to enhance the therapeutical effect of abiraterone acetate on prostate cancer patients who are resistant to abiraterone acetate.
已知miR-143在各种癌细胞和肿瘤中表达下调，通常发挥肿瘤抑制作用。然而，miR-143在介导前列腺癌细胞对醋酸阿比特龙敏感性方面的作用仍未明确。通过miRNA芯片和定量实时PCR（qRT-PCR）测定miRNA的表达水平。通过蛋白质印迹分析评估蛋白质水平。分别通过细胞计数试剂盒-8（CCK-8）测定和流式细胞术测量细胞活力和凋亡。我们发现，与PC3细胞相比，PC3-AbiR细胞中miR-143明显下调。miR-143的过表达在体外和体内均促进PC-AbiR对醋酸阿比特龙的敏感性。我们还发现，miR-143的上调抑制p-JNK（c-Jun氨基末端激酶）并增加p-Bcl2（B细胞淋巴瘤2），促进醋酸阿比特龙诱导的PC3-AbiR细胞凋亡。最后，我们表明，miR-143和醋酸阿比特龙联合使用对荷PC3-AbiR肿瘤小鼠具有最显著的肿瘤抑制作用，并延长了小鼠的存活率。miR-143的上调可能是增强醋酸阿比特龙对醋酸阿比特龙耐药的前列腺癌患者治疗效果的一种新策略。
