Chakraborty Samik, Adhikary Arghya, Mazumdar Minakshi, Mukherjee Shravanti, Bhattacharjee Pushpak, Guha Deblina, Choudhuri Tathagata, Chattopadhyay Samit, Sa Gaurisankar, Sen Aparna, Das Tanya
Division of Molecular Medicine, Bose Institute, Kolkata, West Bengal, India.
Department of Biotechnology, Viswa-Bharati, Santiniketan, West Bengal, India.
PLoS One. 2014 Jun 13;9(6):e99743. doi: 10.1371/journal.pone.0099743. eCollection 2014.
Lung cancer is the leading cause of cancer-related deaths worldwide. Despite decades of research, the treatment options for lung cancer patients remain inadequate, either to offer a cure or even a substantial survival advantage owing to its intrinsic resistance to chemotherapy. Our results propose the effectiveness of capsaicin in down-regulating VEGF expression in non-small cell lung carcinoma (NSCLC) cells in hypoxic environment. Capsaicin-treatment re-activated p53-SMAR1 positive feed-back loop in these cells to persuade p53-mediated HIF-1α degradation and SMAR1-induced repression of Cox-2 expression that restrained HIF-1α nuclear localization. Such signal-modulations consequently down regulated VEGF expression to thwart endothelial cell migration and network formation, pre-requisites of angiogenesis in tumor micro-environment. The above results advocate the candidature of capsaicin in exclusively targeting angiogenesis by down-regulating VEGF in tumor cells to achieve more efficient and cogent therapy of resistant NSCLC.
肺癌是全球癌症相关死亡的主要原因。尽管经过了数十年的研究，但肺癌患者的治疗选择仍然不足，由于其对化疗的固有抗性，既无法提供治愈方法，甚至也无法带来显著的生存优势。我们的研究结果表明，辣椒素在低氧环境下可有效下调非小细胞肺癌（NSCLC）细胞中的VEGF表达。辣椒素处理可重新激活这些细胞中的p53-SMAR1正反馈回路，以促使p53介导的HIF-1α降解以及SMAR1诱导的Cox-2表达抑制，从而抑制HIF-1α的核定位。这种信号调节因此下调了VEGF表达，以阻止内皮细胞迁移和网络形成，而这是肿瘤微环境中血管生成的先决条件。上述结果表明，辣椒素有望通过下调肿瘤细胞中的VEGF来专门靶向血管生成，从而实现对耐药性NSCLC更有效、更有力的治疗。
