Comparison of the therapeutic effects of lobaplatin and carboplatin on retinoblastoma in vitro and in vivo

Abstract

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.

Anti-Gastric Cancer Effect of Purified Omphalia Lapidescens Protein via Regulating the JAK/STAT3 Signaling Pathway

“…Despite the treatment advances have been made over the past 20 years, the prognosis of gastric cancer remains to be poor [15][16]. Nowadays, microarrays and high-throughput bioinformatics technologies, are widely used in drug screening, new drug development, and disease diagnosis [18].…”

In vitro triple culture model of retinoblastoma for pre‐clinical investigations

“…This causes an arrest of cells in the G2/M phase and thereby leads to cell death via apoptosis. [7,23] These molecular cues cascade multiple signaling pathways that govern the miR200 expression. The miR200 family is responsible for the tumor suppression.…”

“…Higher concentrations of carboplatin result in major side effects like nephrotoxicity, ototoxicity, neuropathy, hypomagnesemia, hypersensitive, reactions, and hepatotoxicity. [ 5,7 ] These side effects can be overcome by reducing the drug concentration through the use of monoclonal antibodies (mAbs) as synergistic agents. Recent therapeutic strategies employ mAbs as an additional therapeutic strategy to block specific growth factor receptors, thereby inhibiting tumor progression.…”

Selected platinum complexes in standard and modern anti-cancer therapies

“…Increased sensitivity of cancer cells to radiation and to the pro-apoptotic activity of lobaplatin was revealed in its cumulative action with radiotherapy [67]. The preliminary results of in vitro and in vivo studies show that lobaplatin may have antitumor efficacy higher than carboplatin, with limited nephro-, neuro-and ototoxicity [68]. Nevertheless, a side effect limiting the use of the drug is the found thrombocytopenia [69].…”