Li Xiao-Peng, Zhang Hai-Long, Wang Hui-Juan, Li Yong-Xia, Li Meng, Lu Lian, Wan Yang, Zhou Bai-Ling, Liu Yan, Pan Ying, Wu Xiao-Zhe, Fan Ying-Zi, Yu Chao-Heng, Wei Yu-Quan, Shi Hua-Shan
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Clinical Medical School, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Oncol Rep. 2014 Aug;32(2):650-8. doi: 10.3892/or.2014.3253. Epub 2014 Jun 12.
Radiation therapy is a conventional strategy for treating advanced lung cancer yet is accompanied by serious side-effects. Its combination with other strategies, such as antiangiogenesis and gene therapy, has shown excellent prospects. As one of the potent endogenous vascular inhibitors, endostatin has been widely used in the antiangiogenic gene therapy of tumors. In the present study, LL/2 cells were infected with a recombinant adenovirus encoding endostatin (Ad-endostatin) to express endostatin. The results showed that LL/2 cells infected with the Ad-endostatin efficiently and longlastingly expressed endostatin. In order to further explore the role of Ad-endostatin combined with irradiation in the treatment of cancer, a murine lung cancer model was established and treated with Ad-endostatin combined with low-dose irradiation. The results showed that the combination treatment markedly inhibited tumor growth and metastasis, and prolonged the survival time of the tumor-bearing mice. Furthermore, this significant antitumor activity was associated with lower levels of microvessel density and anoxia factors in the Ad-Endo combined with irradiation group, and with an increased apoptotic index of tumor cells. In addition, no serious side-effects were noted in the combination group. Based on our findings, Ad-endostatin combined with low-dose irradiation may be a rational alternative treatment for lung cancer and other solid tumors.
放射治疗是治疗晚期肺癌的传统策略，但会伴随严重的副作用。它与其他策略（如抗血管生成和基因治疗）联合使用已展现出良好的前景。内皮抑素作为一种有效的内源性血管抑制剂，已广泛应用于肿瘤的抗血管生成基因治疗。在本研究中，LL/2细胞用编码内皮抑素的重组腺病毒（Ad-内皮抑素）感染以表达内皮抑素。结果显示，感染Ad-内皮抑素的LL/2细胞能高效且持久地表达内皮抑素。为了进一步探究Ad-内皮抑素联合放疗在癌症治疗中的作用，建立了小鼠肺癌模型并用Ad-内皮抑素联合低剂量放疗进行治疗。结果表明，联合治疗显著抑制肿瘤生长和转移，并延长了荷瘤小鼠的生存时间。此外，这种显著的抗肿瘤活性与Ad-内皮抑素联合放疗组中较低的微血管密度和缺氧因子水平以及肿瘤细胞凋亡指数增加有关。另外，联合组未观察到严重的副作用。基于我们的研究结果，Ad-内皮抑素联合低剂量放疗可能是肺癌和其他实体瘤合理的替代治疗方法。
