Chou Su-Tze, Ho Bing-Ying, Tai Yu-Ting, Huang Chun-Jen, Chao Wen-Wan
Department of Food and Nutrition, Providence University, Taichung, 433 Taiwan.
Department of Anesthesiology, Wan Fang Hospital, Taipei Medical University, Taipei, 116 Taiwan.
Chin Med. 2020 Jul 29;15:77. doi: 10.1186/s13020-020-00358-2. eCollection 2020.
Cisplatin (CDDP) is a chemotherapeutic drug which also causes adverse side effects. is a traditional Chinese herb belonging to the Labiatae family and has many biological activities. Our previous study indicated that rosmarinic acid (RA) was the most abundant phytochemical in . However, the antioxidant or anti-inflammatory effects of the combined treatment of , RA and CDDP on human renal cell carcinoma (RCC) 786-O cells have not been clearly demonstrated. We aimed to investigate the bioefficacy of hot water extracts of (HWG) and RA in inhibiting RCC 786-O cell activity and its synergism with CDDP against metastatic renal cancer cell.
Bioactivities of the combination treatment of HWG, RA, HWG/CDDP and RA/CDDP were assessed using the MTT assay and transwell migration, and the crude extract/compound efficacy was evaluated using wound healing migration assays, flow cytometry and western blotting.
Our study indicates that CDDP inhibits 786-O cell proliferation and migration and HWG and RA protect against these effects. On the other hand, HWG and RA demonstrate a low cytotoxic effect in human renal proximal tubular epithelial cell line -2 (HK-2 cells). Cell cycle analysis found that HWG/CDDP and RA/CDDP combined treatment exerted cytotoxicity by inducing G2/M arrest and apoptosis. RA in combined with CDDP significantly inhibiting the expression of p-FAK (Tyr 925) in RCC 786-O cells in vitro.
We propose that the inhibition of RA on RCC 786-O cell invasion and migration may partly occur through the downregulation of FAK phosphorylation. The HWG/CDDP and RA/CDDP combined treatments may be effective strategies for intervention of RCC 786-O cell activity.
顺铂(CDDP)是一种化疗药物,也会引起不良副作用。迷迭香是一种属于唇形科的传统中药,具有多种生物活性。我们之前的研究表明,迷迭香酸(RA)是迷迭香中含量最丰富的植物化学物质。然而,迷迭香热水提取物(HWG)、RA与CDDP联合治疗对人肾细胞癌(RCC)786-O细胞的抗氧化或抗炎作用尚未得到明确证实。我们旨在研究HWG和RA抑制RCC 786-O细胞活性的生物功效及其与CDDP对转移性肾癌细胞的协同作用。
采用MTT法和Transwell迁移实验评估HWG、RA、HWG/CDDP和RA/CDDP联合治疗的生物活性,并通过伤口愈合迁移实验、流式细胞术和蛋白质印迹法评估粗提物/化合物的疗效。
我们的研究表明,CDDP抑制786-O细胞增殖和迁移,而HWG和RA可对抗这些作用。另一方面,HWG和RA在人肾近端小管上皮细胞系-2(HK-2细胞)中表现出低细胞毒性作用。细胞周期分析发现,HWG/CDDP和RA/CDDP联合治疗通过诱导G2/M期阻滞和凋亡发挥细胞毒性作用。RA与CDDP联合在体外显著抑制RCC 786-O细胞中p-FAK(Tyr 925)的表达。
我们认为RA对RCC 786-O细胞侵袭和迁移的抑制作用可能部分通过下调FAK磷酸化来实现。HWG/CDDP和RA/CDDP联合治疗可能是干预RCC 786-O细胞活性的有效策略。