Tumor-targeting Salmonella typhimurium A1-R overcomes nab-paclitaxel resistance in a cervical cancer PDOX mouse model

Kentaro Miyake, Takuya Murata, Takashi Murakami, Ming Zhao, Tasuku Kiyuna, Kei Kawaguchi, Kentaro Igarashi, Masuyo Miyake, Thinzar M. Lwin, Chihiro Hozumi, Shin Komatsu, Takashi Kikuchi, Michael Bouvet, Koichiro Shimoya, Shree Ram Singh, Itaru Endo, Robert M. Hoffman

研究成果: Article査読

6 被引用数 (Scopus)

抄録

Purpose: 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. Methods: 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 mm3: G1: untreated group; G2: nab-PTX (i.v., 10 mg/kg, biweekly, 3 weeks); G3: Salmonella typhimurium A1-R (i.v., 5 × 107 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 × 107 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. Results: 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). Conclusions: Salmonella typhimurium A1-R has potential future clinical application to overcome drug resistance in cervical cancer.

本文言語English
ページ(範囲)1683-1690
ページ数8
ジャーナルArchives of Gynecology and Obstetrics
299
6
DOI
出版ステータスPublished - 2019 6 1
外部発表はい

ASJC Scopus subject areas

  • 産婦人科学

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