Adult pleomorphic rhabdomyosarcoma (RMS) is a rare and malignant mesenchymal tumor. Recently, we developed a patient-derived orthotopic xenograft (PDOX) model of adult pleomorphic RMS. In the present study, we evaluated the efficacy of tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R combined with caffeine (CAF) and valproic acid (VPA) on the adult RMS PDOX. An adult pleomorphic RMS cell line was established from the PDOX model. Cell survival after exposure to CAF and VPA was assessed, and the IC₅₀ value was calculated for each drug. The RMS PDOX models were randomized into five groups: untreated control; tumor treated with cyclophosphamide (CPA); tumor treated with CAF + VPA; tumor treated with S. typhimurium A1-R; and tumor treated with S. typhimurium A1-R + CAF + VPA. Tumor size and body weight was measured twice a week. VPA caused a concentration-dependent cytocidal effect. A synergistic effect of combination treatment with CAF was observed against the RMS cell line. For the in vivo study, all treatments significantly inhibited tumor growth compared with the untreated control. S. typhimurium A1-R combined with VPA and CAF was significantly more effective than CPA, VPA combined with CAF, or S. typhimurium A1-R alone and significantly regressed the tumor volume compared with day 0. These results suggest that S. typhimurium A1-R together with VPA and CAF could regresses an adult pleomorphic RMS in a PDOX model and therefore has important future clinical potential.

成人多形性横纹肌肉瘤（RMS）是一种罕见的恶性间质瘤。最近，我们开发了成人多形RMS的患者源性原位异种移植（PDOX）模型。在本研究中，我们评估了针对肿瘤的鼠伤寒沙门氏菌（鼠伤寒沙门氏菌）A1-R联合咖啡因（CAF）和丙戊酸（VPA）对成年RMS PDOX的疗效。从PDOX模型建立了成年的多形RMS细胞系。评估暴露于CAF和VPA后的细胞存活率，并计算每种药物的IC ₅₀值。RMS PDOX模型随机分为五组：未处理的对照组；未处理的对照组；未处理的对照组。用环磷酰胺（CPA）治疗的肿瘤；CAF + VPA治疗的肿瘤；鼠伤寒沙门氏菌治疗的肿瘤A1-R；鼠伤寒沙门氏菌A1-R + CAF + VPA治疗的肿瘤。每周两次测量肿瘤大小和体重。VPA引起浓度依赖性杀细胞作用。观察到与CAF联合治疗对RMS细胞系的协同作用。对于体内研究，与未治疗的对照相比，所有治疗均显着抑制了肿瘤的生长。鼠伤寒沙门氏菌A1-R联合VPA和CAF比单独使用CPA，VPA联合CAF或鼠伤寒沙门氏菌A1-R显着更有效，并且与第0天相比明显降低了肿瘤体积。这些结果表明鼠伤寒沙门氏菌 A1-R与VPA和CAF一起可以使PDOX模型中的成人多形RMS退化，因此具有重要的未来临床潜力。