Hatakeyama Hiroto, Wu Sherry Y, Lyons Yasmin A, Pradeep Sunila, Wang Wanqin, Huang Qian, Court Karem A, Liu Tao, Nie Song, Rodriguez-Aguayo Cristian, Shen Fangrong, Huang Yan, Hisamatsu Takeshi, Mitamura Takashi, Jennings Nicholas, Shim Jeajun, Dorniak Piotr L, Mangala Lingegowda S, Petrillo Marco, Petyuk Vladislav A, Schepmoes Athena A, Shukla Anil K, Torres-Lugo Madeline, Lee Ju-Seog, Rodland Karin D, Fagotti Anna, Lopez-Berestein Gabriel, Li Chun, Sood Anil K
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center (MDACC), Houston, TX 77030, USA.
Department of Cancer Systems Imaging, MDACC, Houston, TX 77030, USA.
Cell Rep. 2016 Nov 1;17(6):1621-1631. doi: 10.1016/j.celrep.2016.10.020.
Even though hyperthermia is a promising treatment for cancer, the relationship between specific temperatures and clinical benefits and predictors of sensitivity of cancer to hyperthermia is poorly understood. Ovarian and uterine tumors have diverse hyperthermia sensitivities. Integrative analyses of the specific gene signatures and the differences in response to hyperthermia between hyperthermia-sensitive and -resistant cancer cells identified CTGF as a key regulator of sensitivity. CTGF silencing sensitized resistant cells to hyperthermia. CTGF small interfering RNA (siRNA) treatment also sensitized resistant cancers to localized hyperthermia induced by copper sulfide nanoparticles and near-infrared laser in orthotopic ovarian cancer models. CTGF silencing aggravated energy stress induced by hyperthermia and enhanced apoptosis of hyperthermia-resistant cancers.
尽管热疗是一种很有前景的癌症治疗方法，但特定温度与临床益处以及癌症对热疗敏感性的预测指标之间的关系仍知之甚少。卵巢癌和子宫癌对热疗的敏感性各不相同。对热疗敏感和耐药癌细胞之间特定基因特征及热疗反应差异的综合分析确定了结缔组织生长因子（CTGF）是敏感性的关键调节因子。CTGF基因沉默使耐药细胞对热疗敏感。在原位卵巢癌模型中，CTGF小干扰RNA（siRNA）处理也使耐药癌症对硫化铜纳米颗粒和近红外激光诱导的局部热疗敏感。CTGF基因沉默加剧了热疗诱导的能量应激，并增强了热疗耐药癌症的细胞凋亡。
