Department of Environmental and Occupational Health, National Cheng Kung University, Medical College, Tainan, Taiwan.
PLoS One. 2012;7(2):e31579. doi: 10.1371/journal.pone.0031579. Epub 2012 Feb 20.
Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells) and PC-3 cells (androgen-independent human prostate cancer cells) were used to investigate the anti-cancer effects of ionizing radiation (IR) combined with arsenic trioxide (ATO) and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS) generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen-independent prostate cancer.
前列腺癌是男性最常见的恶性肿瘤。在本研究中，我们使用 LNCaP（雄激素敏感的人前列腺癌细胞）和 PC-3 细胞（雄激素非依赖性人前列腺癌细胞）来研究电离辐射（IR）联合三氧化二砷（ATO）对前列腺癌的抗癌作用，并在体外和体内确定其潜在机制。我们发现，与单独治疗相比，IR 联合 ATO 增加了对 LNCaP 和 PC-3 人前列腺癌细胞的治疗效果。此外，与单独用 ATO 或 IR 处理相比，联合处理在 PC-3 细胞中显示出增强的活性氧（ROS）生成。联合处理诱导 LNCaP 细胞发生自噬和细胞凋亡，并且主要在 PC-3 细胞中诱导自噬。联合处理诱导的细胞死亡主要是由于 Akt/mTOR 信号通路的抑制。此外，我们发现，用 3-MA 预处理的细胞的联合处理导致 AO 阳性细胞和细胞毒性发生显著变化。在体内研究中，联合治疗具有抗肿瘤生长作用。这些新发现表明，联合治疗不仅是治疗雄激素依赖性前列腺癌的潜在治疗策略，也是治疗雄激素非依赖性前列腺癌的潜在治疗策略。
