Matsumoto Yasunori, Miwa Shinji, Zhang Yong, Hiroshima Yukihiko, Yano Shuya, Uehara Fuminari, Yamamoto Mako, Toneri Makoto, Bouvet Michael, Matsubara Hisahiro, Hoffman Robert M, Zhao Ming
AntiCancer, Inc., San Diego, California; Department of Surgery, University of California San Diego, San Diego, California; Department of Frontier Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
J Cell Biochem. 2014 Nov;115(11):1996-2003. doi: 10.1002/jcb.24871.
We report here the efficacy of tumor-targeting Salmonella typhimurium A1-R (A1-R) on mouse models of disseminated and metastatic ovarian cancer. The proliferation-inhibitory efficacy of A1-R on human ovarian cancer cell lines (SKOV-3-GFP, OVCAR-3-RFP) was initially demonstrated in vitro. Orthotopic and dissemination mouse models of ovarian cancer were made with the human ovarian cancer cell line SKOV-3-GFP. After tumor implantation, the mice were treated with A1-R (5 × 10(7) colony-forming units [CFU], i.v.), and there were no severe adverse events observed. In the orthotopic model, tumor volume after treatment was 276 ± 60.8 mm(3), compared to 930 ± 342 mm(3) in the untreated control group (P = 0.022). There was also a significant difference in survival between treated mice and untreated mice in a peritoneal dissemination model (P = 0.005). The results of this report demonstrate that A1-R is effective for highly aggressive human ovarian cancer in metastatic and dissemination mouse models and suggest its clinical potential for this highly treatment-resistant disease.
我们在此报告肿瘤靶向性鼠伤寒沙门氏菌A1-R（A1-R）对播散性和转移性卵巢癌小鼠模型的疗效。A1-R对人卵巢癌细胞系（SKOV-3-GFP、OVCAR-3-RFP）的增殖抑制疗效最初在体外得到证实。用人卵巢癌细胞系SKOV-3-GFP构建卵巢癌原位和播散小鼠模型。肿瘤植入后，用A1-R（5×10⁷集落形成单位[CFU]，静脉注射）治疗小鼠，未观察到严重不良事件。在原位模型中，治疗后肿瘤体积为276±60.8 mm³，而未治疗的对照组为930±342 mm³（P = 0.022）。在腹膜播散模型中，治疗小鼠和未治疗小鼠的生存率也有显著差异（P = 0.005）。本报告结果表明，A1-R对转移性和播散性小鼠模型中的高侵袭性人卵巢癌有效，并提示其对这种高度耐药疾病的临床应用潜力。
