Matsumoto Yasunori, Miwa Shinji, Zhang Yong, Zhao Ming, Yano Shuya, Uehara Fuminari, Yamamoto Mako, Hiroshima Yukihiko, Toneri Makoto, Bouvet Michael, Matsubara Hisahiro, Tsuchiya Hiroyuki, Hoffman Robert M
AntiCancer, Inc, San Diego, CA, USA.
Department of Surgery, University of California San Diego, San Diego, CA, USA.
Oncotarget. 2015 May 10;6(13):11369-77. doi: 10.18632/oncotarget.3607.
Peritoneal disseminated cancer is highly treatment resistant. We here report the efficacy of intraperitoneal (i.p.) administration of tumor-targeting Salmonella typhimurium A1-R in a nude mouse model of disseminated human ovarian cancer. The mouse model was established by intraperitoneal injection of the human ovarian cancer cell line SKOV3-GFP. Seven days after implantation, mice were treated with S. typhimurium A1-R via intravenous (i.v.) or i.p. administration at the same dose, 5 × 10(7) CFU, once per week. Both i.v. and i.p. treatments effected prolonged survival compared with the untreated control group (P=0.025 and P<0.001, respectively). However, i.p. treatment was less toxic than i.v.
Tumor-specific targeting of S. typhimurium A1-R was confirmed with bacterial culture from tumors and various organs and tumor or organ colony formation after i.v. or i.p. injection. Selective tumor targeting was most effective with i.p. administration. The results of the present study show S. typhimurium A1-R has promising clinical potential for disseminated ovarian cancer, especially via i.p. administration.
腹膜播散性癌具有高度的治疗抵抗性。我们在此报告在人卵巢癌播散性裸鼠模型中腹腔内（i.p.）注射肿瘤靶向性鼠伤寒沙门氏菌A1-R的疗效。通过腹腔注射人卵巢癌细胞系SKOV3-GFP建立小鼠模型。植入后7天，小鼠以相同剂量5×10⁷CFU通过静脉内（i.v.）或腹腔内给药，每周一次，接受鼠伤寒沙门氏菌A1-R治疗。与未治疗的对照组相比，静脉内和腹腔内治疗均使生存期延长（分别为P = 0.025和P < 0.001）。然而，腹腔内治疗的毒性低于静脉内治疗。
通过对肿瘤和各个器官进行细菌培养以及静脉内或腹腔内注射后肿瘤或器官菌落形成，证实了鼠伤寒沙门氏菌A1-R的肿瘤特异性靶向。腹腔内给药时选择性肿瘤靶向最为有效。本研究结果表明，鼠伤寒沙门氏菌A1-R在播散性卵巢癌中具有良好的临床潜力，尤其是通过腹腔内给药。
