Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, Selangor, Malaysia.
UKM Medical Molecular Biology Institute (UMBI), UKM Medical Centre, Kuala Lumpur, Malaysia.
Integr Cancer Ther. 2019 Jan-Dec;18:1534735419880258. doi: 10.1177/1534735419880258.
This study aimed to evaluate the antitumor enhancing effect of bromelain consumption on 4T1-challenged mice treated with cisplatin. Mice challenged with 4T1 triple-negative breast cancer cells received water, bromelain, cisplatin, or bromelain + cisplatin treatment for 28 days. Tumor size was measured, and lung metastasis was evaluated by clonogenic assay. Expression of tumor inflammatory genes of the harvested tumor was quantified by polymerase chain reaction array and ELISA (enzyme-linked immunosorbent assay). : All treatments significantly reduced the size of tumor and lung metastasis, with combination treatment showing the best effect. Also, bromelain alone and combination treatment showed downregulation of the expression of tumor inflammatory genes (Gremlin [GREM1], interleukin 1β [IL-1β], interleukin-4 [IL-4], nuclear factor κB subunit 1 [NFκB1], and prostaglandin-endoperoxide synthase 2 [PTGS2]), tumor nitric oxide level, and serum IL-1β, and IL-4 levels. On the other hand, cisplatin treatment increased the expression of selected inflammatory markers. This study suggests that bromelain treatment could potentiate the antitumor effect of cisplatin on triple-negative breast cancer 4T1 cells through modulating the tumor environmental inflammation.
本研究旨在评估菠萝蛋白酶消耗对顺铂治疗的 4T1 荷瘤小鼠的抗肿瘤增强作用。用 4T1 三阴性乳腺癌细胞攻击的小鼠接受水、菠萝蛋白酶、顺铂或菠萝蛋白酶+顺铂治疗 28 天。测量肿瘤大小，并通过集落形成试验评估肺转移。通过聚合酶链反应阵列和 ELISA（酶联免疫吸附试验）定量测定收获肿瘤的肿瘤炎症基因的表达。：所有治疗均显著降低肿瘤和肺转移的大小，联合治疗效果最佳。此外，单独使用菠萝蛋白酶和联合治疗均显示肿瘤炎症基因（Gremlin [GREM1]、白细胞介素 1β [IL-1β]、白细胞介素 4 [IL-4]、核因子 κB 亚单位 1 [NFκB1]和前列腺素内过氧化物合酶 2 [PTGS2]）的表达下调、肿瘤一氧化氮水平以及血清 IL-1β 和 IL-4 水平降低。另一方面，顺铂治疗增加了选定炎症标志物的表达。本研究表明，菠萝蛋白酶治疗可能通过调节肿瘤环境炎症增强顺铂对三阴性乳腺癌 4T1 细胞的抗肿瘤作用。
