Better to be alone than in bad company: The antagonistic effect of cisplatin and crizotinib combination therapy in non-small cell lung cancer

Steen, Nele Van Der; Deben, Christophe; Deschoolmeester, Vanessa; Wouters, An; Lardon, Filip; Rolfo, Christian; Germonpré, Paul; Giovannetti, Elisa; Peters, Godefridus J.; Pauwels, Patrick

doi:10.5306/wjco.v7.i6.425

Cited by 8 publications

(3 citation statements)

References 43 publications

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“…Interestingly, a recent study investigating the effect of crizotinib in combination with cisplatin in 4 NSCLC cell lines showed remarkable antagonism among the 4 cell lines discouraging crizotinib and cisplatin combination in NSCLC. 57 Collectively, the effect of combined crizotinib and chemotherapy in cancer is variable and the level of interaction could be affected by the type of chemotherapeutic agents, type of cancer cells, and possible other factors.…”

Section: Discussionmentioning

confidence: 99%

Crizotinib, a MET inhibitor, inhibits growth, migration, and invasion of breast cancer cells in vitro and synergizes with chemotherapeutic agents

Ayoub¹,

Al-Shami²,

Alqudah³

et al. 2017

OTT

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MET is a receptor tyrosine kinase known for its pleiotropic effects in tumorigenesis. Dysregulations of MET expression and/or signaling have been reported and determined to be associated with inferior outcomes in breast cancer patients rendering MET a versatile candidate for targeted therapeutic intervention. Crizotinib is a multi-targeted small-molecule kinase inhibitor for MET, ALK, and ROS1 kinases. This study evaluated the anti-proliferative, cytotoxic, anti-migratory, and anti-invasive effects of crizotinib in breast cancer cells in vitro. Cell viability was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colorimetric assay. In vitro wound-healing assay was used to examine the effect of crizotinib on breast cancer cell migration. The expressions of Ki-67, MET, and phospho-MET receptors were characterized using immunofluorescence staining. Results showed that crizotinib has significant anti-proliferative activity on all mammary tumor cells with IC50 values of 5.16, 1.5, and 3.85 µM in MDA-MB-231, MCF-7, and SK-BR-3 cells, respectively. Crizotinib induced cytotoxic effects in all breast cancer cells examined. Combined treatment of small dose of crizotinib with paclitaxel or doxorubicin exhibited a highly synergistic inhibition of growth of MDA-MB-231 and MCF-7 cells with combination index values <1 while no significant effect was observed in SK-BR-3 cells compared with individual compounds. Treatment with crizotinib demonstrated a remarkable reduction in the expression of Ki-67 protein in all 3 tested cell lines. Crizotinib inhibited migration and invasion of MDA-MB-231 cells in a dose-dependent fashion. Crizotinib reduced MET receptor activation in MDA-MB-231 cells when treated at effective concentrations. In conclusion, crizotinib suppressed proliferation, migration, and invasion of breast cancer cells in vitro. The results of this study demonstrated that combined treatment of crizotinib with chemotherapeutic agents resulted in a synergistic growth inhibition of specific breast cancer cell lines.

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Section: Discussionmentioning

confidence: 99%

Crizotinib, a MET inhibitor, inhibits growth, migration, and invasion of breast cancer cells in vitro and synergizes with chemotherapeutic agents

Ayoub¹,

Al-Shami²,

Alqudah³

et al. 2017

OTT

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show abstract

“…In fact, potential drug interactions, especially antagonism, have received intense attention from researchers. An increasing body of evidence indicates the antagonistic effects of various drug-combinations on treatment of cancers such as esophageal cancer and non-small-cell lung cancer [ 64 , 65 ]. Therefore, healthcare professionals should be aware of the doses of concomitant drugs used and request that patients provide all their medications, including prescriptions, over-the-counter medications, and herbal supplements in order to avoid possible drug interactions.…”

Section: Discussionmentioning

confidence: 99%

Combined Administration of Escitalopram Oxalate and Nivolumab Exhibits Synergistic Growth-Inhibitory Effects on Liver Cancer Cells through Inducing Apoptosis

Chen

Huang

et al. 2023

IJMS

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Liver cancer is one of the most lethal malignant cancers worldwide. However, the therapeutic options for advanced liver cancers are limited and reveal scant efficacy. The current study investigated the effects of nivolumab (Niv) and escitalopram oxalate (Esc) in combination on proliferation of liver cancer cells both in vitro and in vivo. Significantly decreased viability of HepG2 cells that were treated with Esc or Niv was observed in a dose-dependent manner at 24 h, 48 h, and 72 h. Administration of Esc (50 μM) + Niv (20 μM), Esc (75 μM) + Niv (5 μM), and Esc (75 μM) + Niv (20 μM) over 24 h exhibited synergistic effects, inhibiting the survival of HepG2 cells. Additionally, treatment with Esc (50 μM) + Niv (1 μM), Esc (50 μM) + Niv (20 μM), and Esc (75 μM) + Niv (20 μM) over 48 h exhibited synergistic effects, inhibiting the survival of HepG2 cells. Finally, treatment with Esc (50 μM) + Niv (1 μM), Esc (50 μM) + Niv (20 μM), and Esc (75 μM) + Niv (20 μM) for 72 h exhibited synergistic effects, inhibiting HepG2 survival. Com-pared with controls, HepG2 cells treated with Esc (50 μM) + Niv (20 μM) exhibited significantly increased sub-G1 portion and annexin-V signals. In a xenograft animal study, Niv (6.66 mg/kg) + Esc (2.5 mg/kg) significantly suppressed the growth of xenograft HepG2 tumors in nude mice. This study reports for the first time the synergistic effects of combined administration of Niv and Esc for inhibiting HepG2 cell proliferation, which may provide an alternative option for liver cancer treatment.

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“…Its activation stimulates cells to break inter-cellular bonds and migrate. The disruption of signal transduction and constant activation of the receptor is an important event taking place in a variety of neoplasms, including adenocarcinoma of stomach and oesophagus (Chan et al, 2016), non-small cell lung cancer (Van Der Steen et al, 2016) and ovarian cancer (Moran-Jones, 2016). During carcinogenesis, mutations in the c-MET gene occur, enabling activation of the receptor even in the absence of a ligand.…”

Section: Introductionmentioning

confidence: 99%

Expression of c-MET Protein in Various Subtypes of Hepatocellular Adenoma Compared to Hepatocellular Carcinoma and Non-Neoplastic Liver in Human Tissue

Szparecki,

Ilczuk,

Gabzdyl

et al. 2017

Fol. Biol.

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Hepatocellular adenoma (HA) is a benign neoplasm of the liver, whose aetiopathogenesis is little known. Newest research allowed dividing all cases into three types based on molecular characteristics: inflammatory HA, HA with HNF1A mutation, β-catenin- mutated HA. The clinical significance of HA is chiefly due to the possibility of malignant transformation into hepatocellular carcinoma (HCC). The aim of the present study was to immunohistochemically assess the expression pattern and level of c-MET protein in hepatocellular adenoma (taking into account its status of Wnt/β-catenin pathway functioning) and intertwining the results into a wider pattern of expression in non-neoplastic liver and hepatocellular carcinoma of various histological grades. It was found that expression of c-MET in poorly-differentiated HCC was significantly higher than in non-neoplastic liver and well- to moderately-differentiated HCC. The expression in HA was variable and differed between molecular subtypes of this neoplasm: inflammatory and HNF1A mutation-associated type are characterized by overexpression of c-MET to an extent comparable with poorly-differentiated HCC, whereas Wnt/β-catenin dysfunction-associated type lacks overexpression, and the amount of c-MET protein accumulated in its cells is similar to the levels in non-neoplastic tissue and well- to moderately-differentiated HCC. These findings suggest that c-MET overexpression in HA is not an early event in hepatocarcinogenesis, but constitutes a divergent molecular pathway leading to neoplastic change compared to overexpression observed in the late stages of tumour progression.

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Better to be alone than in bad company: The antagonistic effect of cisplatin and crizotinib combination therapy in non-small cell lung cancer

Cited by 8 publications

References 43 publications

Crizotinib, a MET inhibitor, inhibits growth, migration, and invasion of breast cancer cells in vitro and synergizes with chemotherapeutic agents

Crizotinib, a MET inhibitor, inhibits growth, migration, and invasion of breast cancer cells in vitro and synergizes with chemotherapeutic agents

Combined Administration of Escitalopram Oxalate and Nivolumab Exhibits Synergistic Growth-Inhibitory Effects on Liver Cancer Cells through Inducing Apoptosis

Expression of c-MET Protein in Various Subtypes of Hepatocellular Adenoma Compared to Hepatocellular Carcinoma and Non-Neoplastic Liver in Human Tissue

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