Erol Seyit Ahmet, Sel Görker, Harma Mehmet İbrahim, Harma Müge, Tekin İshak Özel
Clinic of Obstetrics and Gynecology, Ankara City Hospital, Ankara, Turkey
Clinic of Obstetrics and Gynecology, Zonguldak Bülent Ecevit University Health Practice and Research Hospital, Zonguldak, Turkey
J Turk Ger Gynecol Assoc. 2020 Sep 3;21(3):171-179. doi: 10.4274/jtgga.galenos.2020.2019.0199. Epub 2020 Jul 6.
The aim was to investigate the effectiveness of pegylated liposomal doxorubicin (PLD), beta-carotene, and a combination of PLD and beta-carotene on JAR and JEG-3 human choriocarcinoma (CC) cell lines for the treatment of CC.
JAR and JEG-3 cells were cultured. PLD and beta-carotene trial groups were determined with different doses (for single drug trial; PLD 1, 2, 5 μg/mL and beta-carotene 1, 5, 10 μg/mL, and for combined drug trial; all PLD doses combined with beta-carotene 5 μg/mL). Drugs were administered to cultures simultaneously, and 72 hours later the cells were detached using trypsin-ethylenediamine tetraacetic acid solution. The percentage of apoptotic cells was determined by flow cytometry after annexin V staining. One set of the supernatant was collected before trypsin application to investigate beta-human chorionic gonadotropin (β-hCG) and hyperglycosylated hCG (H-hCG) levels. Statistical analyses of the apoptotic ratios were performed using Shapiro-Wilk, Kruskal-Wallis and Mann-Whitney U tests.
Apoptosis increased in JAR and JEG-3 cultures after treatment with all doses of PLD (p<0.05). A single application of each betacarotene dose increased apoptosis in JAR cells (p<0.05) but had no apoptotic effects on JEG-3 cells. In the PLD and beta-carotene combination group, apoptosis increased in both JAR and JEG-3 cells (p<0.05).
To our knowledge, this is the first investigation of the effectiveness of PLD, beta-carotene, and PLD + beta-carotene combination therapy in two different CC cell lines. PLD is a promising chemotherapeutic drug, and beta-carotene can be used as a novel non-chemotherapeutic agent for treatment of CC. Based on the results of this study, vitamin A supplementation may have promise as a preventive measure. However, these data need support from animal experiments and clinical trials.
研究聚乙二醇化脂质体阿霉素（PLD）、β-胡萝卜素以及PLD与β-胡萝卜素联合用药对JAR和JEG-3人绒毛膜癌（CC）细胞系治疗CC的有效性。
培养JAR和JEG-3细胞。确定PLD和β-胡萝卜素试验组的不同剂量（单药试验；PLD为1、2、5μg/mL，β-胡萝卜素为1、5、10μg/mL；联合用药试验；所有PLD剂量与5μg/mLβ-胡萝卜素联合）。将药物同时加入培养物中，72小时后用胰蛋白酶-乙二胺四乙酸溶液消化细胞。用膜联蛋白V染色后通过流式细胞术测定凋亡细胞的百分比。在应用胰蛋白酶前收集一组上清液以检测β-人绒毛膜促性腺激素（β-hCG）和高糖基化hCG（H-hCG）水平。使用Shapiro-Wilk检验、Kruskal-Wallis检验和Mann-Whitney U检验对凋亡率进行统计分析。
用所有剂量的PLD处理后，JAR和JEG-3培养物中的凋亡增加（p<0.05）。各剂量的β-胡萝卜素单次应用均增加了JAR细胞中的凋亡（p<0.05），但对JEG-3细胞无凋亡作用。在PLD与β-胡萝卜素联合组中，JAR和JEG-3细胞中的凋亡均增加（p<0.05）。
据我们所知，这是首次对PLD、β-胡萝卜素以及PLD +β-胡萝卜素联合疗法在两种不同CC细胞系中的有效性进行研究。PLD是一种有前景的化疗药物，β-胡萝卜素可作为治疗CC的新型非化疗药物。基于本研究结果，补充维生素A可能有望作为一种预防措施。然而，这些数据需要动物实验和临床试验的支持。
