Lobaplatin suppresses proliferation and peritoneal metastasis of colorectal cancer in a preclinical model

Shan, Lina; Bai, Bingjun; Lv, Yiming; Xie, Binbin; Huang, Xuefeng; Zhu, Hongbo

doi:10.1016/j.biopha.2018.09.063

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…This finding indicates that both carboplatin and lobaplatin inhibit tumor growth and that the therapeutic effects of lobaplatin were more prominent than those of carboplatin. In previous studies, lobaplatin has been shown to be effective in inhibiting esophageal squamous cell carcinoma and colorectal cancer tumors (11,31). Thus, it can be concluded that lobaplatin exerts similar inhibitory effects on RB.…”

Section: Discussionmentioning

confidence: 91%

“…Several preclinical studies have established the antitumor activity of lobaplatin and have investigated the underlying mechanisms in multiple malignancies ( 11 , 29 - 31 ); for example, lobaplatin has been found to induce caspase-dependent apoptosis and to increase the Bax/Bcl-2 ratio in esophageal squamous cell carcinoma ( 29 ). Lobaplatin may prevent cell cycle progression; similarly, it may play significant roles in stimulating apoptosis, altering the proteome and impeding invasion and migration.…”

Section: Discussionmentioning

confidence: 99%

“…The representative 3rd-generation platinum drug, lobaplatin (D-19466; 1,2-diamminomethylcyclobu-tane-platinum(II) lactate), can cause DNA damage via GG and AG intrastrand crosslinking to form DNA-drug adducts and to inhibit tumor activity, which may influence the expression of certain genes in tumor cells ( 10 ). Lobaplatin has exhibited promising therapeutic effects in several clinical studies; for example, it has been found to suppress proliferation and peritoneal metastasis in a preclinical model of colorectal cancer ( 11 ), to inhibit gastric cancer cells by inducing apoptosis ( 12 ), and to arrest cells in S phase and trigger apoptosis in the context of human non-small cell lung cancer ( 13 ). Furthermore, lobaplatin can be used to overcome the drug resistance associated with cisplatin observed in several types of cancer as it exhibits lower toxicity compared with cisplatin ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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“…In addition, lobaplatin is appropriate for intraoperative intraperitoneal chemotherapy due to its lighter inhibitory effects on the neurological system, hematological system and gastrointestinal system. A preclinical model research [23] conduct that the survival rate of suspended CRC cells was only 16.3% when treated with 100 mg/L lobaplatin for 6 hours. Therefore, 0.1 g/L lobaplatin intraperitoneal chemotherapy for 6 hours during surgery was performed in order to obtain a strong e cacy on CRC patients with suspicious PM in the present study, while the dosage of 50 mg/person was far lower than the recommended dosage (50 mg/m2), without any obvious toxic side reaction.…”

Section: Discussionmentioning

confidence: 99%

Effect and Safety of Intraoperative Intraperitoneal Chemotherapy on Patients Suffering From Colorectal Cancer.

Shang

Wang

Yang

et al. 2021

Preprint

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BackgroundColorectal cancer (CRC), the third most commonly diagnosed malignant neoplasm and the third most common cause of carcinoma-related mortality, continues to be a major international health problem. And approximately 33% of patients suffer from recurrence after radical surgery. Free malignant cells implanting in the peritoneum is generally accepted for present purposes. We did the study with the aim of evaluating the effects and safety of Intraoperative intraperitoneal chemotherapy (IOC) on patients suffering from colorectal cancer.MethodsIn total, 357 patients who went through colorectal radical surgery were considered eligible between September 23rd, 2017 to December 31st, 2018. 179 patients were treated with surgery alone, and 178 patients received surgery plus IOC. Clinical characteristics, operative findings, postoperative short-term outcomes and Disease- Free survival (DFS) were compared between the 2 groups in the selected population.ResultThe present research involves 357 patients (224 men and 133 women) who underwent surgery alone (n = 179) or surgery plus IOC (n = 178), with a mean (SD) age of 61.9 (10.4) years in the surgery alone group and 61.9 (9.1) in the surgery plus IOC group (P = .52). No significant differences were witnessed between the two groups in surgery-related information and postoperative complications. In patients with stage II colorectal cancer, the Disease- Free 1, 2and 3 years survival rates of surgery alone group were 98%, 91% and 86% respectively; and 96%, 94% and 81% respectively for surgery combined with IOC group (P = .82, Kaplan-Meier log-rank). In stage Ⅲ CRC patients, the survival rate analysis (Kaplan-Meier) showed a 82%, 68% and 61% Disease- Free survival of surgery alone group and a 94%, 85% and 82% of surgery plus IOC group after 1, 2 and 3 years, respectively (P = .002, Kaplan-Meier log rank).ConclusionsIn the present study, we have found that surgery plus IOC generated a favorable prognosis for stage Ⅲ CRC patients but not stage Ⅱ without any side-effects when the dosage of lobaplatin was 0.1 g/L. As a new, safe, and simple procedure, IOC therapy is easily performed anywhere and does not require any special devices or techniques. Thus, IOC is a promising and exciting therapeutic strategy for patients with CRC.

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“…14,15 Although these drugs are effective in the treatment of PC, the absolute advantage of any specific drug cannot be derived. 16…”

Section: Introductionmentioning

confidence: 99%

Hyperthermic intraperitoneal chemotherapy with recombinant mutant human TNF-α and raltitrexed in mice with colorectal-peritoneal carcinomatosis

Gong

Song

Wang

et al. 2020

Exp Biol Med (Maywood)

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Peritoneum is one of the most common metastatic sites of colorectal cancer (CRC). It has been reported that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) prolongs the lifespan of patients with peritoneal carcinomatosis of colorectal origin (CRC-PC), while the drugs used for HIPEC are limited. We investigated the application of recombinant mutant human tumor necrosis factor-α (rmhTNF) combined with raltitrexed in the HIPEC treatment in a mice model with CRC-PC. In vitro, we detected the cytotoxicity and apoptosis of human colorectal cancer cells by 3–(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, Western blot, and TdT-mediated dUTP Nick End Labeling (TUNEL) assay. In vivo, we established xenograft models of CRC-PC and assessed the antitumor effect by in vivo imaging, peritoneal cancer index scoring, and TUNEL assay. The results showed that the combination of rmhTNF and raltitrexed under hyperthermia with a temperature of 42°C inhibited the growth of colorectal cancer cells significantly in vitro, and after HIPEC treatments with rmhTNF and raltitrexed, peritoneal tumor growth was prohibited in vivo. Our findings about the efficacy of rmhTNF and raltitrexed used for HIPEC to treat CRC-PC will provide experimental data and basis for their potential clinical application. Impact statement Colorectal peritoneal carcinomatosis exhibits poor prognosis and presents a treatment challenge. At present, the main treatment is surgery, supplemented by hyperthermic intraperitoneal chemotherapy (HIPEC), but the drugs used for HIPEC are limited. Our study found that the combination of recombinant mutant human TNF-α (rmhTNF) and raltitrexed (RTX) under hyperthermia with a temperature of 42°C had antitumor effect both in vitro and vivo. The findings will provide experimental data and basis for the potential clinical application of rmhTNF and RTX, which might offer patients a new choice of therapeutic drugs.

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Lobaplatin suppresses proliferation and peritoneal metastasis of colorectal cancer in a preclinical model

Cited by 9 publications

References 34 publications

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

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

Effect and Safety of Intraoperative Intraperitoneal Chemotherapy on Patients Suffering From Colorectal Cancer.

Hyperthermic intraperitoneal chemotherapy with recombinant mutant human TNF-α and raltitrexed in mice with colorectal-peritoneal carcinomatosis

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