AntiCancer Inc., San Diego, CA, USA.
Department of Surgery, University of California, San Diego, CA, USA.
Arch Gynecol Obstet. 2019 Jun;299(6):1683-1690. doi: 10.1007/s00404-019-05147-3. Epub 2019 Apr 5.
Cervical cancer is a recalcitrant disease. To help overcome this problem, we previously established a patient-derived orthotopic xenograft (PDOX) model of cervical cancer. In the previous study, we found the tumor to be resistant to nab-paclitaxal (nab-PTX). We also previously developed the tumor-targeting bacteria Salmonella typhimurium A1-R (S. typhimurium A1-R). The aim of the present study was to investigate the efficacy of S. typhimurium A1-R to overcome nab-PTX resistance in the cervical cancer PDOX model.
Cervical-cancer tumor fragments were implanted orthotopically into the neck of the uterus of nude mice. The cervical-cancer PDOX models were randomized into the following four groups after the tumor volume reached 60 mm: G1: untreated group; G2: nab-PTX (i.v., 10 mg/kg, biweekly, 3 weeks); G3: Salmonella typhimurium A1-R (i.v., 5 × 10 CFU/body, weekly, 3 weeks); G4: nab-PTX combined with Salmonella typhimurium A1-R (nab-PTX, 10 mg/kg, i.v., biweekly, 3 weeks; S. typhimurium A1-R, 5 × 10 CFU/body, i.v., weekly, 3 weeks). Each group comprised eight mice. All mice were sacrificed on day 22. Tumor volume was measured on day 0 and day 22. Body weight was measured twice a week.
Nab-PTX and Salmonella typhimurium A1-R did not show significant efficacy as monotherapy compared to the control group (P = 0.564 and P = 0.120, respectively). In contrast, nab-PTX combined with Salmonella typhimurium A1-R significantly suppressed tumor growth compared to the untreated control group and nab-PTX group (P < 0.001 and P = 0.026, respectively).
Salmonella typhimurium A1-R has potential future clinical application to overcome drug resistance in cervical cancer.
宫颈癌是一种顽固的疾病。为了帮助克服这一问题，我们之前建立了宫颈癌患者来源的原位异种移植（PDOX）模型。在之前的研究中，我们发现肿瘤对nab-紫杉醇（nab-PTX）有耐药性。我们之前还开发了肿瘤靶向细菌鼠伤寒沙门氏菌 A1-R（S. typhimurium A1-R）。本研究旨在探讨 S. typhimurium A1-R 克服宫颈癌 PDOX 模型中 nab-PTX 耐药性的疗效。
将宫颈肿瘤组织片段原位植入裸鼠子宫颈部。肿瘤体积达到 60mm 后，将宫颈癌 PDOX 模型随机分为以下四组：G1：未治疗组；G2：nab-PTX（iv，10mg/kg，每两周一次，共 3 周）；G3：鼠伤寒沙门氏菌 A1-R（iv，5×10CFU/体，每周一次，共 3 周）；G4：nab-PTX 联合鼠伤寒沙门氏菌 A1-R（nab-PTX，10mg/kg，iv，每两周一次，共 3 周；鼠伤寒沙门氏菌 A1-R，5×10CFU/体，iv，每周一次，共 3 周）。每组 8 只小鼠。所有小鼠于第 22 天处死。于第 0 天和第 22 天测量肿瘤体积。每周测量两次体重。
与对照组相比，nab-PTX 和鼠伤寒沙门氏菌 A1-R 单独治疗均无明显疗效（P=0.564 和 P=0.120）。相比之下，nab-PTX 联合鼠伤寒沙门氏菌 A1-R 与未治疗对照组和 nab-PTX 组相比，显著抑制肿瘤生长（P<0.001 和 P=0.026）。
鼠伤寒沙门氏菌 A1-R 具有克服宫颈癌药物耐药性的潜在临床应用前景。
