Cancer Biology Division, School of Biotechnology, Kalinga Institute of Industrial Technology (KIIT), Deemed to be University, Bhubaneswar, Odisha, India.
School of Applied Sciences (Chemistry), Kalinga Institute of Industrial Technology (KIIT), Deemed to be University, Bhubaneswar, Odisha, India.
Nanomedicine. 2022 Feb;40:102502. doi: 10.1016/j.nano.2021.102502. Epub 2021 Nov 26.
Cancer stem cells (CSCs) are the tumor cell subpopulations that can self-renew, differentiate, initiate and maintain tumor growth. CSCs are frequently drug-resistant, resulting in tumor recurrence, metastasis, and angiogenesis. Herein, using in vitro oral squamous cell carcinoma (OSCC) CSCs and in vivo xenograft mice model, we have systematically studied the apoptotic potentiality of quinacrine-gold hybrid nanoparticle (QAuNP) and its underlying mechanism after NIR irradiation. QAuNP + NIR caused DNA damage and induced apoptosis in SCC-9-CSCs by deregulating mitochondrial membrane potential (ΔΨm) and activation of ROS. Upregulation of CASPASE-3 and DR-5/DR-4 and reduction of heat shock protein (HSP-70) up to 5-fold were also noticed upon the treatment. The increased expression of DR-5 and CASPASE-3 and decreased expression of HSP-70, CD-44 and Ki-67 were also noted in the xenograft mice treated with QAuNP + NIR + TRAIL. Thus, data suggest that the combined treatment enhances apoptosis in OSCC-CSCs by modulating HSP-70 in the DISC.
肿瘤干细胞(CSCs)是能够自我更新、分化、启动和维持肿瘤生长的肿瘤细胞亚群。CSCs 通常具有耐药性,导致肿瘤复发、转移和血管生成。在此,我们使用体外口腔鳞状细胞癌(OSCC)CSCs 和体内异种移植小鼠模型,系统研究了 NIR 照射后吖啶橙-金杂化纳米粒子(QAuNP)的凋亡潜力及其潜在机制。QAuNP+NIR 通过扰乱线粒体膜电位(ΔΨm)和激活 ROS,导致 SCC-9-CSCs 中的 DNA 损伤并诱导细胞凋亡。还注意到在处理过程中 CASPASE-3 和 DR-5/DR-4 的上调以及热休克蛋白(HSP-70)的下调高达 5 倍。在用 QAuNP+NIR+TRAIL 处理的异种移植小鼠中也观察到 DR-5 和 CASPASE-3 的表达增加以及 HSP-70、CD-44 和 Ki-67 的表达减少。因此,数据表明,联合治疗通过调节 DISC 中的 HSP-70 增强了 OSCC-CSCs 中的细胞凋亡。