School of Life Sciences, Central University of Gujarat, Gandhinagar, Gujarat, India; Cancer and Radiation Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA.
Toxicol In Vitro. 2017 Oct;44:74-84. doi: 10.1016/j.tiv.2017.06.016. Epub 2017 Jun 17.
Natural Killer T (NKT) cells based cancer immunotherapy is an evolving area of cancer therapy, but tumors escape from this treatment modality by altering CD1d expression and its antigen presentation pathway. Here, we have studied the relation of CD1d expression in various breast cancer cell lines to their viability and progression. We observed a novel phenomenon that CD1d expression level increases with the progressive stage of the cancer. A small molecule, zerumbone (ZER) caused down-regulation of CD1d that was accompanied by breast cancer cell growth in vitro. The growth inhibitory effect of ZER against breast cancer cells was augmented by treatment with anti-CD1d mAb. This effect was mediated by G1-phase cell cycle arrest and apoptosis induction coupled with an increase in mitochondrial membrane depolarization. CD1d expression and cell proliferation were inhibited by both CD1d siRNA and ZER. The α-galactosylceramide, a ligand for CD1d, showed increased CD1d expression as well as cell proliferation which was opposite to the effects of ZER. This study shows that, CD1d overexpression is associated with the progressive stages of breast cancer and ZER could be an adjuvant to potentiate cancer immunotherapy.
自然杀伤 T（NKT）细胞癌症免疫疗法是癌症治疗中一个不断发展的领域，但肿瘤通过改变 CD1d 的表达及其抗原呈递途径来逃避这种治疗方式。在这里，我们研究了各种乳腺癌细胞系中 CD1d 表达与它们的活力和进展的关系。我们观察到一种新的现象，即 CD1d 的表达水平随着癌症的进展阶段而增加。一种小分子，莪术醇（ZER）导致 CD1d 的下调，伴随着体外乳腺癌细胞的生长。用抗 CD1d mAb 处理增强了 ZER 对乳腺癌细胞的生长抑制作用。这种作用是通过 G1 期细胞周期阻滞和凋亡诱导与线粒体膜去极化增加介导的。CD1d siRNA 和 ZER 均抑制 CD1d 表达和细胞增殖。CD1d 的配体 α-半乳糖神经酰胺显示出增加的 CD1d 表达以及细胞增殖，这与 ZER 的作用相反。这项研究表明，CD1d 的过表达与乳腺癌的进展阶段有关，ZER 可能是增强癌症免疫疗法的辅助剂。
