Wang Zhigang, Lu Pingfang, Liang Zhu, Zhang Zhanfei, Shi Weicheng, Cai Xiaobi, Chen Chunyuan
a The Affiliated Hospital of Guangdong Medical University , Zhanjiang , Guangdong , China and.
b Guangdong General Hospital of Armed Police Forces , Guangzhou , Guangdong , China.
Growth Factors. 2015;33(5-6):337-46. doi: 10.3109/08977194.2015.1088533. Epub 2015 Oct 2.
Insulin-like growth factor 1 receptor (IGF1R) is a tyrosine kinase receptor implicated in tumourigenesis that may be an attractive target for anti-cancer treatment. In this study, the expression and clinical significance of IGF1R were investigated in serum and lung cancer tissues from small cell lung cancinoma (SCLC). We also compared the effect of IGF1R up-regulation and IGF1R inhibition on viability and apoptosis of NCI-H446 cells. We found the concentration of IGF1R in blood serum was significantly increased and positive IGF1R protein in cancer tissue was more prevalent in SCLC. A statistically significant correlation among IGF1R-positve tumors, lymph node metastasis and local invasion was discussed. Furthermore, IGF1R overexpression lead to an increase of cell survival and suppressed cell apoptosis, IGF1R silencing mediated by RNAi abrogate this response of NCI-H446 cells. Our results further demonstrated that the effects of these treatments may be assigned to the effective inhibition of lung cancer cells from Akt/P27(Kip1) pathway in IGF-1R signaling. These features may have important implications for future anti-IGF1R therapeutic approaches.
胰岛素样生长因子1受体（IGF1R）是一种与肿瘤发生相关的酪氨酸激酶受体，可能是抗癌治疗的一个有吸引力的靶点。在本研究中，我们调查了小细胞肺癌（SCLC）患者血清和肺癌组织中IGF1R的表达及其临床意义。我们还比较了IGF1R上调和抑制对NCI-H446细胞活力和凋亡的影响。我们发现，SCLC患者血清中IGF1R浓度显著升高，癌组织中IGF1R蛋白阳性更为普遍。讨论了IGF1R阳性肿瘤、淋巴结转移和局部侵袭之间的统计学显著相关性。此外，IGF1R过表达导致细胞存活增加并抑制细胞凋亡，RNAi介导的IGF1R沉默消除了NCI-H446细胞的这种反应。我们的结果进一步证明，这些治疗的效果可能归因于对IGF-1R信号通路中肺癌细胞Akt/P27（Kip1）途径的有效抑制。这些特征可能对未来的抗IGF1R治疗方法具有重要意义。
