Mekkawy Ahmed H, Pillai Krishna, Badar Samina, Akhter Javed, Ke Kevin, Valle Sarah J, Morris David L
Department of Surgery, St. George Hospital Kogarah, NSW 2217, Australia.
Mucpharm Pty Ltd Australia.
Am J Cancer Res. 2021 May 15;11(5):2252-2263. eCollection 2021.
The combinations of Bromelain and Acetylcysteine (BromAc) with cytotoxics such as Gemcitabine, 5-Fluorouracil or Oxaliplatin have shown a dramatic reduction in IC50 values in a variety of cancers, including colon cancer, suggesting the possibility of effective treatment without undesired side effects. In the current study, we investigated whether a similar effect is present using the colorectal cell line LS174T. Animals after acclimatization were randomized and allocated equally in the groups for the different studies (safety, dose-escalation, and efficacy). Drugs were delivered by the intraperitoneal route and animals were monitored for wellbeing. Separately, an efficacy study was conducted with intraperitoneal drug delivery after intraperitoneal tumor induction. At the termination of the experiment, tumors and other tissues were collected for evaluation. BromAc was safe when delivered intraperitoneally in a rat model at the concentrations used. Subsequent investigations of these adjuvants in combination with Gemcitabine, Oxaliplatin, and 5-Fluorouracil in mice were also proven to be safe. Preliminary efficacy studies with Oxaliplatin and 5-Fluorouracil on tumor growth (LS174T) were negative. Gemcitabine was assessed with BromAc showing an almost 71% tumor inhibition compared to controls. This study indicates that Gemcitabine at 2 mg/kg in combination with BromAc 3 mg/300 mg/Kg was effective and safe, supporting its potential for future clinical application.
菠萝蛋白酶与乙酰半胱氨酸(BromAc)的组合,与吉西他滨、5-氟尿嘧啶或奥沙利铂等细胞毒性药物联合使用时,在包括结肠癌在内的多种癌症中显示出IC50值显著降低,这表明有可能实现有效治疗且无不良副作用。在本研究中,我们使用结肠直肠癌细胞系LS174T研究是否存在类似效果。适应环境后的动物被随机分组,并平均分配到不同研究(安全性、剂量递增和疗效)的组中。药物通过腹腔内途径给药,并监测动物的健康状况。另外,在腹腔内诱导肿瘤后,通过腹腔内给药进行疗效研究。实验结束时,收集肿瘤和其他组织进行评估。在大鼠模型中,以所用浓度腹腔内给药时,BromAc是安全的。随后在小鼠中对这些佐剂与吉西他滨、奥沙利铂和5-氟尿嘧啶联合使用的研究也被证明是安全的。奥沙利铂和5-氟尿嘧啶对肿瘤生长(LS174T)的初步疗效研究结果为阴性。吉西他滨与BromAc联合使用时,与对照组相比显示出近71%的肿瘤抑制率。本研究表明,2mg/kg的吉西他滨与3mg/300mg/Kg的BromAc联合使用是有效且安全的,支持其未来临床应用的潜力。