Antitumor effects of FP3 in combination with capecitabine on PDTT xenograft models of primary colon carcinoma and related lymphatic and hepatic metastases

Jin, Ketao; Lan, Huanrong; Xie, Bojian; He, Kuifeng; Xu, Zhenzhen; Li, Guangliang; Han, Na; Teng, Lisong; Cao, Feng

doi:10.4161/cbt.20556

Cited by 7 publications

(8 citation statements)

References 24 publications

(29 reference statements)

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“…The PDTX models of gastric cancer were successfully established, with histological examinations of H&E sections from the third generation xenografts of both Met-GC1 and Met-GC2 showing poorly differentiated adenocarcinoma consistent with the original clinical cancer (Figure 1 a, b). We had previously ascertained that PDTX xenografts could retain the histopathologic and molecular characteristics of the original clinical cancer [ 20 , 21 ]. The expressions of cMet and HER2 were evaluated, since trastuzumab has been recommended as a treatment for patients with Her2-overexpressing gastric cancer.…”

Section: Resultsmentioning

confidence: 99%

“…Hence, PDTX models have been increasingly used as a tool for the preclinical assessment of anticancer drugs. Our group has previously established PDTX models of colon carcinoma, and successfully evaluated a novel VEGF-targeted agent [ 20 , 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Patient-derived human tumor xenograft (PDTX) models, which closely retain the histopathologic, genetic and phenotypic features of the original clinical cancer, offer a powerful tool for the study of tumor biology and the evaluation of anticancer drugs. Recently, we established PDTX models of colon carcinoma, and successfully evaluated a novel molecular drug [ 20 , 21 ]. In the present study, we evaluated the antitumor efficacy of luteolin in cMet-overexpressing PDTX models as well as in gastric cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

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Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer

Lü

et al. 2015

J Transl Med

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BackgroundAberrated activation of cMet in gastric cancer contributes to tumor growth, angiogenesis and metastasis. cMet-overexpressing gastric cancer has a poor prognosis because of high tumor metastasis and limited therapeutic options. Luteolin is a common dietary flavonoid with antitumor properties. However, the antitumor effect of luteolin on cMet-overexpressing gastric cancer remain unclear.MethodsTwo cMet-overexpressing patient-derived human tumor xenograft (PDTX) models of gastric cancer were established, and treated with luteolin or vehicle to evaluate the antitumor effects of luteolin. Tumor specimens were subjected to H&E staining and immunohistochemistry. MKN45 and SGC7901 cells that show high cMet expression were treated with varying concentrations of luteolin and evaluated by western blot, cell viability, apoptosis, migration, and invasion assays.ResultsLuteolin inhibited the tumor growth in cMet-overexpressing PDTX models. Immunohistochemistry demonstrated that expression of cMet, MMP9 and Ki-67 were significantly down-regulated. Luteolin inhibited proliferation, promoted apoptosis and reduced the invasiveness of MKN45 and SGC7901 cells. Western blot revealed that luteolin promoted the activation of apoptosis-related proteins, caspase-3 and PARP-1, and down-regulated the invasion-associated protein, MMP9. Further studies demonstrated that luteolin decreased the expression and phosphorylation of cMet, and downstream phosphorylation of Akt and ERK. In addition, luteolin down-regulated phosphorylated Akt independently of cMet. Blocking Akt and/or ERK with the PI3K inhibitor, LY294002, or the ERK inhibitor, PD98059, induced down-regulation of MMP9 and up-regulation of cleaved caspase-3 and PARP-1, resembling the effects of luteolin.ConclusionsOur findings ,for the first time, demonstrate that luteolin exerts marked antitumor effects in cMet-overexpressing PDTX models of gastric cancer, through a mechanism likely involving cMet/Akt/ERK signaling. These findings indicate that luteolin may act as a potential therapeutic option for cMet-overexpressing gastric cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0398-z) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer

Lü

et al. 2015

J Transl Med

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“…Our results are of importance to predict the effi ciency of chemotherapy with this drug. The effects of capecitabine and 5-FU on expression of enzymes for fl uoropyrimidine metabolism (e.g., TP) were studied previously [4,11]. Despite the estimated pharmacodynamics of 5-FU, there are no data that TP activity decreases over a relatively short period (6 h) after single treatment wit 5-FU.…”

Section: Resultsmentioning

confidence: 99%

Effect of 5-Fluorouracil on Thymidine Phosphorylase Activity in Model Experiment

et al. 2016

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Variations in thymidine phosphorylase activity in rat liver were studied in 1, 3, 6, 12, and 24 h after intraperitoneal bolus injection of 5-fluorouracil. Enzyme activity was measured by HPLC. A 2-fold decrease in enzyme activity was observed 3 h after 5-fluorouracil administration and persisted for 12 h. This additional effect of the cytostatic should be taken into account in choosing chemotherapy protocol.

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“…The PDX models of primary and metastatic tumors have been established in our laboratory and have been used for antitumor drug sensitivity assays which could guide clinical practice of personalized cancer therapy (4,(42)(43)(44)(45)(46)(47)(48). Based on our clinical and laboratorial experience, it is practical to obtain primary or metastatic breast cancer for PDX model use even if the spreading of the tumor is extensive.…”

Section: Patient-derived Tumor Xenograft Patient-derived Tumor Xenogrmentioning

confidence: 99%

Personalized and Dynamic Therapy for Breast Cancer: A Preclinical Perspective

Lan¹,

Gu²,

Li³

et al. 2017

JTMR

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Breast cancer is one of the leading causes of mortality worldwide. Genomic studies have provided key insights into how breast cancer develop, evolve, metastasize, recurrence and respond to treatment. The advance of next-generation sequencing (NGS) and bioinformatics has led to an unprecedented view of the breast cancer genome and its evolution, and made the dynamic monitoring of recurrence and selective evolution of breast cancer during therapy a reality. Here we illustrate a proposed preclinical strategy of personalized and dynamic therapy for breast cancer based on the technologies of NGS and patient-derived tumor xenograft (PDX) model. The goal of this strategy is to provide a preclinical model of personalized and dynamic therapy for breast cancer to improve patients' outcomes.

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Antitumor effects of FP3 in combination with capecitabine on PDTT xenograft models of primary colon carcinoma and related lymphatic and hepatic metastases

Abstract: (2012) Antitumor effects of FP3 in combination with capecitabine on PDTT xenograft models of primary colon carcinoma and related lymphatic and hepatic metastases, Cancer Biology & Therapy, 13:9, 737-744,

Cited by 7 publications

References 24 publications

Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer

Luteolin exerts a marked antitumor effect in cMet-overexpressing patient-derived tumor xenograft models of gastric cancer

Effect of 5-Fluorouracil on Thymidine Phosphorylase Activity in Model Experiment

Personalized and Dynamic Therapy for Breast Cancer: A Preclinical Perspective

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