Abstract:
Unlike MCF-7 cells, MDA-MB-231 cells are unresponsive to hormone therapy and often show resistance to chemotherapy and radiotherapy. Here, the antiproliferative effect of biocompatible montmorillonite (Mt) nanosheets on MDA-MB-231 and MCF-7 human breast cancer cells was evaluated by MTT assay, flow cytometry, and qRT-PCR. The results showed that the Mt IC50 for MDA-MB-231 and MCF-7 cells in a fetal bovine serum (FBS)-free medium was ~50 and ~200 µg/mL, and in 10% FBS medium ~400 and ~2000 µg/mL, respectively. Mt caused apoptosis in both cells by regulating related genes including Cas-3, P53, and P62 in MDA-MB-231 cells and Bcl-2, Cas-8, Cas-9, P53, and P62 in MCF-7 cells. Also, Mt arrested MCF-7 cells in the G0/G1 phase by altering Cyclin-D1 and P21 expression, and caused sub-G1 arrest and necrosis in both cells, possibly through damaging the mitochondria. However, fewer gene expression changes and more sub-G1 arrest and necrosis were observed in MDA-MB-231 cells, confirming the higher vulnerability of MDA-MB-231 cells to Mt. Furthermore, MDA-MB-231 cells appeared to be much more vulnerable to Mt compared to other cell types, including normal lung fibroblast (MRC-5), colon cancer (HT-29), and liver cancer (HepG2) cells. The higher vulnerability of MDA-MB-231 cells to Mt was inferred to be due to their higher proliferation rate. Notably, Mt cytotoxicity was highly dependent on both the Mt concentration and serum level, which favors Mt for the local treatment of MDA-MB-231 cells. Based on these results, Mt can be considered as an antiproliferative nanoagent against MDA-MB-231 cells and may be useful in the development of local nanoparticle-based therapies.
摘要:
与MCF-7细胞不同,MDA-MB-231细胞对激素治疗无反应,通常对化疗和放疗表现出抗性。这里,通过MTT法评价生物相容性蒙脱石(Mt)纳米片对MDA-MB-231和MCF-7人乳腺癌细胞的抗增殖作用,流式细胞术,和qRT-PCR。结果表明,在无胎牛血清(FBS)的培养基中,MDA-MB-231和MCF-7细胞的MtIC50为〜50和〜200µg/mL,在10%FBS培养基中~400和~2000微克/毫升,分别。Mt通过调节MDA-MB-231细胞中的Cas-3,P53和P62以及MCF-7细胞中的Bcl-2,Cas-8,Cas-9,P53和P62等相关基因引起两种细胞的凋亡。此外,Mt通过改变Cyclin-D1和P21的表达而将MCF-7细胞阻滞在G0/G1期,并导致两个细胞的亚G1期停滞和坏死,可能是通过破坏线粒体.然而,在MDA-MB-231细胞中观察到更少的基因表达变化和更多的亚G1期停滞和坏死,证实MDA-MB-231细胞对Mt.此外,与其他细胞类型相比,MDA-MB-231细胞似乎更容易受到Mt的影响。包括正常肺成纤维细胞(MRC-5),结肠癌(HT-29),和肝癌(HepG2)细胞。推断MDA-MB-231细胞对Mt的脆弱性较高是由于它们的增殖率较高。值得注意的是,Mt细胞毒性高度依赖于Mt浓度和血清水平,这有利于Mt对MDA-MB-231细胞的局部治疗。基于这些结果,Mt可以被认为是针对MDA-MB-231细胞的抗增殖纳米剂,并且可以用于开发基于局部纳米颗粒的疗法。