Department of Interventional Radiology and Vascular Anomalies, Guangzhou Women and Children's Medical Center of Guangzhou Medical University, Guangzhou, Guangdong 510627, P.R. China.
Int J Oncol. 2020 Sep;57(3):697-706. doi: 10.3892/ijo.2020.5085. Epub 2020 Jun 22.
Retinoblastoma (RB) is one of the most aggressive malignancies affecting infants and children. Platinum drugs are commonly used in the treatment of RB; however, their efficacy is often compromised by drug resistance and severe toxicity. The present study aimed to investigate and compare the toxicity and antitumor activity of the third‑generation platinum drugs, carboplatin and lobaplatin, in vitro and in vivo. The Y79 RB cell line was treated with carboplatin or lobaplatin in vitro and then used to establish xenografts in immunodeficient nude mice in vivo; the effects of pharmacological doses of these drugs were then assessed. High concentrations of carboplatin and lobaplatin markedly inhibited Y79 RB cell proliferation in vitro. In addition, the lobaplatin group exhibited higher proportions of early‑stage apoptotic cells than the carboplatin group, while no significant differences in the proportions of cells in the S phase were observed between the 2 groups, as shown by flow cytometry. Significant changes in the E2F1/Cdc25a/Cdk2 pathway in the RB cells were detected by RNA‑seq following carboplatin or lobaplatin intervention. RT‑qPCR, immunofluorescence and immunohistochemical analyses in vivo and in vitro demonstrated that the trends of drug‑induced inhibition of tumor pathological changes may have been regulated through the E2F1/Cdc25a/Cdk2 pathway, and that lobaplatin was more effective than carboplatin in controlling tumors in vivo. On the whole, the findings of the present study demonstrate that lobaplatin is associated with lower cytotoxicity and exerts more prominent therapeutic effects than carboplatin on Y79 RB cells in vitro and in mice in vivo.
视网膜母细胞瘤 (RB) 是影响婴儿和儿童的最具侵袭性的恶性肿瘤之一。铂类药物常用于 RB 的治疗；然而，它们的疗效常因耐药性和严重毒性而受到影响。本研究旨在比较第三代铂类药物卡铂和洛铂在体外和体内的毒性和抗肿瘤活性。将 Y79 RB 细胞系用卡铂或洛铂处理，然后在免疫缺陷裸鼠体内建立异种移植瘤，评估这些药物的药理学剂量的作用。高浓度的卡铂和洛铂明显抑制 Y79 RB 细胞在体外的增殖。此外，与卡铂组相比，洛铂组中早期凋亡细胞的比例更高，而流式细胞术显示两组细胞在 S 期的比例无显著差异。RNA-seq 检测到卡铂或洛铂干预后 RB 细胞中 E2F1/Cdc25a/Cdk2 通路的显著变化。RT-qPCR、免疫荧光和免疫组织化学分析在体内和体外均表明，药物诱导的肿瘤病理变化抑制趋势可能通过 E2F1/Cdc25a/Cdk2 通路调节，洛铂在体内控制肿瘤的效果优于卡铂。总的来说，本研究的结果表明，洛铂的细胞毒性较低，与卡铂相比，在体外和体内对 Y79 RB 细胞具有更显著的治疗效果。
