Pandey Richa, Chiu Chien-Chih, Wang Li-Fang
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, No. 100 Shih-Chuan first Road, Kaohsiung 80708, Taiwan.
Department of Biotechnology, Kaohsiung Medical University, No. 100 Shih-Chuan first Road, Kaohsiung 80708, Taiwan.
Mol Pharm. 2024 Mar 4;21(3):1364-1381. doi: 10.1021/acs.molpharmaceut.3c01040. Epub 2024 Jan 31.
Immunotherapy has emerged as a promising approach for cancer treatment, and the use of microRNAs (miRNAs) as therapeutic agents has gained significant attention. In this study, we investigated the effectiveness of immunotherapy utilizing miRNA34a and Jurkat T cells in inducing cell death in non-small-cell lung cancer cells, specifically A549 cells. Moreover, we explored the impact of Jurkat T cell activation and miRNA34a delivery using iron oxide nanorods (IONRs) on the killing of cancer cells. A549 cells were cocultured with both activated and inactivated Jurkat T cells, both before and after the delivery of miRNA34a. Surprisingly, our results revealed that even inactive Jurkat T cells were capable of inducing cell death in cancer cells. This unexpected observation suggested the presence of alternative mechanisms by which Jurkat T cells can exert cytotoxic effects on cancer cells. We stimulated Jurkat T cells using anti-CD3/CD28 and analyzed their efficacy in killing A549 compared to that of the inactive Jurkat T cells in conjunction with miRNA34a. Our findings indicated that the activation of Jurkat T cells significantly enhanced their cytotoxic potential against cancer cells compared to their inactive counterparts. The combined treatment of A549 cells with activated Jurkat T cells and miRNA34a demonstrated the highest level of cancer cell death, suggesting a synergistic effect between Jurkat T cell activation and miRNA therapy. Besides the apoptosis mechanism for the Jurkat T cells' cytotoxic effects on A549 cells, we furthermore investigated the ferroptosis pathway, which was found to have an impact on the cancer cell killing due to the presence of miRNA34a and IONRs as the delivery agent inside the cancer cells.
免疫疗法已成为一种很有前景的癌症治疗方法,将微小RNA(miRNA)用作治疗剂已受到广泛关注。在本研究中,我们研究了利用miRNA34a和Jurkat T细胞进行免疫疗法在诱导非小细胞肺癌细胞(特别是A549细胞)死亡方面的有效性。此外,我们还探讨了使用氧化铁纳米棒(IONR)激活Jurkat T细胞和递送miRNA34a对癌细胞杀伤的影响。在递送miRNA34a之前和之后,将A549细胞与活化和未活化的Jurkat T细胞共培养。令人惊讶的是,我们的结果表明即使是未活化的Jurkat T细胞也能够诱导癌细胞死亡。这一意外发现表明存在Jurkat T细胞对癌细胞发挥细胞毒性作用的替代机制。我们使用抗CD3/CD28刺激Jurkat T细胞,并分析它们与未活化的Jurkat T细胞联合miRNA34a相比对A549细胞的杀伤效果。我们的研究结果表明与未活化的Jurkat T细胞相比,Jurkat T细胞的活化显著增强了它们对癌细胞的细胞毒性潜力。活化的Jurkat T细胞与miRNA34a联合处理A549细胞显示出最高水平的癌细胞死亡,表明Jurkat T细胞活化与miRNA疗法之间存在协同作用。除了Jurkat T细胞对A549细胞的细胞毒性作用的凋亡机制外,我们还进一步研究了铁死亡途径,发现由于miRNA34a和作为递送剂的IONR存在于癌细胞内而对癌细胞杀伤有影响。