Laboratory of Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.
Oncol Rep. 2012 Dec;28(6):2009-15. doi: 10.3892/or.2012.2039. Epub 2012 Sep 17.
Intratumoral regions of low extracellular pH and low nutrition are common features of solid tumors. Although cancer cells normally die when they are removed from their environment, a small population of cells survive. In the present study, the subline LNCaP-F10, of the prostate cancer cell line LNCaP, was isolated and its low pH/low nutrient-resistant properties were examined. LNCaP-F10 cells were grown under low-pH/low-nutrient conditions, which caused cell death of the LNCaP cells. The cell death was associated with oligonucleosomal DNA fragmentation and poly (ADP-ribose) polymerase (PARP) cleavage, indicating that low-pH/low-nutrient induced apoptosis in these cells. Significant differences in the expression of BCL2, BIRC5 and DAPK1 were detected between LNCaP-F10 and LNCaP cells. Tumor growth caused by implantation of LNCaP-F10 cells into the renal subcapsular space of nude mice in the absence or presence of prostate stromal cell stimulation was greater than that caused by implantation of LNCaP cells. LNCaP-F10 cells were resistant to apoptosis induced by an environment of low-pH/low-nutrient in vitro, and displayed malignant potential in vivo.
肿瘤内低细胞外 pH 值和低营养区域是实体瘤的常见特征。尽管癌细胞通常在脱离其环境时会死亡，但一小部分细胞会存活下来。在本研究中，前列腺癌细胞系 LNCaP 的亚系 LNCaP-F10 被分离出来，并检查了其耐低 pH 值/低营养的特性。LNCaP-F10 细胞在低 pH 值/低营养条件下生长，这导致 LNCaP 细胞死亡。细胞死亡与寡核苷酸体 DNA 片段化和多聚（ADP-核糖）聚合酶（PARP）裂解有关，表明低 pH 值/低营养诱导这些细胞发生细胞凋亡。在 LNCaP-F10 和 LNCaP 细胞之间检测到 BCL2、BIRC5 和 DAPK1 的表达存在显著差异。将 LNCaP-F10 细胞植入裸鼠肾被膜下腔，无论是否存在前列腺基质细胞刺激，肿瘤生长均大于植入 LNCaP 细胞的情况。LNCaP-F10 细胞在体外耐低 pH 值/低营养环境诱导的细胞凋亡，并在体内显示出恶性潜能。
