Department of Obstetrics and Gynecology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, China.
Department of Health Science, Graduate School of Medical, Osaka University, Osaka, Japan.
Bioengineered. 2021 Dec;12(1):2087-2094. doi: 10.1080/21655979.2021.1931643.
Choriocarcinoma (CC) is a gestational trophoblastic tumor secondary to a gravid or non-gravid pregnancy. It is characterized by rapid growth, high invasion, and high metastatic potential and chemotherapy resistance that significantly affect survival rate of CC patients. Insulin is implicated in alleviation of chemotherapy resistance in CC. However, the mechanism of reversing resistance in CC has not been explored. Our purpose was to explore insulin effect on 5-fluorouracil (5-FU) resistance in CC and elucidate its potential mechanism and . CKK-8, colony formation, Transwell, and flow cytometry were used to detect the effect of insulin on 5-FU resistance in CC cells JEG-3 and JARS. Xenograft mice were used to evaluate the effect of insulin on 5-FU resistance. Results showed that insulin combined with 5-FU suppressed cell viability by 30% in JEG-3 and 43% in JAR compared with 5-FU alone in 72 h. What's more, insulin combined with 5-FU promoted cell apoptosis, inhibited cell proliferation, migration, and phosphorylation of survivin at residue threonine 34 (Thr34) and drug resistance-related proteins, P-GP and MRP1 levels ( < 0.05). experiment showed Insulin combined with 5-FU suppressed tumor volume by 35% compared with 5-FU alone and 73% compared with control in CC xenograft mice. In summary, the findings of this study show that insulin reversed chemoresistance of CC cells to 5-FU by inhibiting phosphorylation of survivin. Development of a therapeutic strategy that combines insulin with the chemotherapeutic agent 5-FU has a great potential in improving survival of CC patients.
绒癌（CC）是一种妊娠或非妊娠滋养细胞肿瘤，其特征是生长迅速、侵袭性高、转移潜能高、化疗耐药，显著影响 CC 患者的生存率。胰岛素可减轻 CC 化疗耐药性。然而，逆转 CC 耐药的机制尚未得到探索。我们的目的是探讨胰岛素对 CC 中 5-氟尿嘧啶（5-FU）耐药性的影响，并阐明其潜在机制。CCK-8、集落形成、Transwell 和流式细胞术用于检测胰岛素对 CC 细胞 JEG-3 和 JARS 中 5-FU 耐药性的影响。异种移植小鼠用于评估胰岛素对 5-FU 耐药性的影响。结果表明，与单独使用 5-FU 相比，胰岛素联合 5-FU 在 72 h 时使 JEG-3 中的细胞活力降低 30%，在 JAR 中降低 43%。更重要的是，胰岛素联合 5-FU 促进细胞凋亡，抑制细胞增殖、迁移和生存素丝氨酸 34 位（Thr34）磷酸化以及耐药相关蛋白 P-糖蛋白和多药耐药相关蛋白 1 水平（<0.05）。实验表明，与单独使用 5-FU 相比，胰岛素联合 5-FU 使 CC 异种移植小鼠的肿瘤体积抑制 35%，与对照组相比抑制 73%。总之，本研究结果表明，胰岛素通过抑制生存素的磷酸化逆转了 CC 细胞对 5-FU 的化疗耐药性。将胰岛素与化疗药物 5-FU 联合开发的治疗策略具有提高 CC 患者生存率的巨大潜力。
