Koraneekit Amonrat, Limpaiboon Temduang, Sangka Arunnee, Boonsiri Patcharee, Daduang Sakda, Daduang Jureerut
Centre for Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
Department of Clinical Microbiology, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
Oncol Lett. 2018 May;15(5):7397-7402. doi: 10.3892/ol.2018.8256. Epub 2018 Mar 13.
Cervical cancer (CxCa) is a major health problem globally and is associated with the presence of human papillomavirus infection. Cisplatin (CDDP) is a platinum-based chemotherapeutic agent. Owing to its side effects and drug-resistance, novel anticancer agents with lower toxicity, including caffeic acid (CFC), are of interest. However, the effects of CDDP and CFC in combination are, to the best of our knowledge, uninvestigated. The present study investigated the effectiveness of CDDP and CFC in combination and its mechanism of action on four human cervical cancer cell lines, which were compared with the normal kidney Vero cell line. Cell viability was evaluated using a sulforhodamine B assay. Caspase-Glo assay kits, measuring the activity of caspases-3, -7, -8 and -9, were used to detect caspase activation in HeLa and CaSki cell lines in response to CDDP and CFC in combination. The results revealed that CDDP and CFC alone reduced the proliferation of HeLa, CaSki, SiHa and C33A cell lines. Treatment with CFC exhibited no significant cytotoxicity towards Vero cells. In addition, CDDP-CFC significantly inhibited cell growth of HeLa and CaSki cell lines. In HeLa and CaSki cell lines, a combination index <1 for CDDP and CFC indicated the synergistic growth inhibition; the combination of the two also significantly increased expression of caspase-3, -7 and -9. In conclusion, CFC may be a candidate anticancer agent that, when use in combination, may increase the therapeutic efficacy of CDDP.
宫颈癌是全球主要的健康问题，与人乳头瘤病毒感染有关。顺铂是一种铂类化疗药物。由于其副作用和耐药性，包括咖啡酸在内的低毒性新型抗癌药物受到关注。然而，据我们所知，顺铂和咖啡酸联合使用的效果尚未得到研究。本研究调查了顺铂和咖啡酸联合使用的有效性及其对四种人宫颈癌细胞系的作用机制，并与正常肾Vero细胞系进行了比较。使用磺酰罗丹明B测定法评估细胞活力。使用Caspase-Glo检测试剂盒测量半胱天冬酶-3、-7、-8和-9的活性，以检测HeLa和CaSki细胞系中对顺铂和咖啡酸联合使用的半胱天冬酶激活情况。结果显示，单独使用顺铂和咖啡酸均可降低HeLa、CaSki、SiHa和C33A细胞系的增殖。咖啡酸处理对Vero细胞无明显细胞毒性。此外，顺铂-咖啡酸显著抑制HeLa和CaSki细胞系的细胞生长。在HeLa和CaSki细胞系中，顺铂和咖啡酸的联合指数<1表明具有协同生长抑制作用；两者联合还显著增加了半胱天冬酶-3、-7和-9的表达。总之，咖啡酸可能是一种候选抗癌药物，与顺铂联合使用时可能会提高其治疗效果。
