CLDN18-ARHGAP26 function in gastric cancer and be a new therapeutic target by ABCG2 and ABCB1 pathway

Li, Jing; Zheng, Xiu Ting; Jia, Jianguang; Xie, Bingteng; Zhang, Chen-Song; Wang, Hu; Li, Hongbo; Ma, Jiachi

doi:10.1590/fst.54821

Cited by 3 publications

(4 citation statements)

References 28 publications

(35 reference statements)

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“…Untreatment: U87 cells without sample treatment; Geniposide: U87 cells treated with 100 μg/mL geniposide solution; LC-NBRC101979: U87 cells treated with 10 6 CFU/mL LC-NBRC101979 solution; Geniposide + LC-NBRC101979: U87 cells treated with 100 μg/mL geniposide and 10 6 CFU/mL LC-NBRC101979 solution. caspase family, oncogenes like c-myc, and the tumor suppressor gene p53, are relatively conservative among species (Lee et al, 2005;Li et al, 2022). Most anticancer drugs cause apoptosis by activating corresponding apoptosis pathways, such as those of the Bcl-2 family proteins, which play an important role in cell death and are reflected by a rise in the Bax/Bcl-2 ratio.…”

Section: Discussionmentioning

confidence: 99%

Lactobacillus casei enhances the apoptosis inducing effect of geniposide on U87 human glioma cells in vitro

et al. 2023

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The goal of this work was to clarify the mechanism of action of Lactobacillus casei on genipin in triggering glioma apoptosis. DPPH and ABTS free radicals could be successfully eliminated by geniposide, LC-NBRC101979 (Lactobacillus casei), and geniposide + LC-NBRC101979. Geniposide and LC-NBRC101979 had effects that were stronger when combined than when taken alone. Geniposide, LC-NBRC101979, and Geniposide + LC-NBRC101979 did not have any detrimental effects on healthy epithelial cells HBE, but they greatly decreased the growth of U87 glioma cells, according to cell studies. Additionally, the combination of geniposide and LC-NBRC101979 had a stronger inhibitory impact than either drug alone. Results from qPCR revealed that in U87 cells, geniposide, LC-NBRC101979, and eniposide + LC-NBRC101979 could up-regulate caspase-3, COX-2, p53, c-myc, p21 mRNA expression and down-regulate Bcl-2, NF-κB expression. According to the results of the study on the effects of oxidative stress on cells, geniposide, LC-NBRC101979, and geniposide combined with LC-NBRC101979 can decrease the levels of MDA, LDH, and NO in normally damaged epithelial cells caused by oxidative stress and increase the levels of CAT, SOD, GSH-Px, and T-AOC. According to HPLC data, LC-NBRC101979 was able to convert the majority of geniposide into geniposide. It is clear that LC-NBRC101979 may enhance geniposide's inhibitory impact on glioma.

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Section: Discussionmentioning

confidence: 99%

Lactobacillus casei enhances the apoptosis inducing effect of geniposide on U87 human glioma cells in vitro

et al. 2023

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“…It has been reported in the literature that Helicobacter pylori causes gastric cancer, which is more likely to be related to hypergastrinemia (Waldum & Fossmark, 2021). In addition, some other related influencing factors include people's smoking, alcoholism, heavy oil and heavy salt eating habits in daily life, as well as the expression of genetic mutations (Li et al, 2022b). Traditional Chinese medicine believes that the occurrence of gastric cancer is the result of the combined action of multiple factors, and the deficiency of righteousness and the disorder of the viscera are the internal causes of the disease.…”

Section: Discussionmentioning

confidence: 99%

Effects of Jiawei Huangqi Guizhi Decoction on the expression of GAS, MTL, GC, and TGF-β3 signaling pathways in CAG rats

CHEN

Cao

et al. 2023

Food Sci. Technol

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To study the effect of Jiawei Huangqi Guizhi Decoction on gastrointestinal hormones and TGF-β3 signal pathways in rats with chronic atrophic gastritis (CAG). The model was created by methylnitrosoguanidine (MNNG) comprehensive method. After successful modeling, it was divided into three groups: model group (MC group), frolic acid group (AC group), modified Huangqi Guizhi Decoction high dose group (HH group), modified Huangqi Guizhi Decoction middle dose group (HM group), and modified Huangqi Guizhi Decoction low dose group (HL group). Gastric pathology was observed by HE staining. The levels of gastrin (GAS) and motilin (MTL) in rat serum were detected by ELISA assay. After HE staining, the histopathological sections were analyzed. Inflammatory factors infiltration and disorder of mucosal epithelial cells were found in the model group, which were improved to some extent after administration. According to the pathological chart analysis and score of rats in each group, compared with the model group, the gastric tissue damage of rats in each administration group has been improved in different degrees, among which the pathological scores of HH and HM groups were lower, and the corresponding damage degree was smaller. According to the test results of ELISA, Jiawei Huangqi Guizhi Decoction could reduce the contents of GAS, TGF-β3, and increase MTL abundance in the serum of rats, thus accelerating the apoptosis of tumor cells and inhibiting cancer. Jiawei Huangqi Guizhi Decoction played a positive role in preventing the occurrence of gastric cancer through reducing the concentrations of GAS and TGF-β3 in serum, and increasing the concentration of MLT in serum. This results provided a new treatment idea for CAG.

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“…Fonte-Adaptada de ZHANG et al, 2021ARHGAP26 está localizado no interior da citomembrana e regula a proliferação celular, apoptose a nível translacional (JARIUS et al, 2013, JING et al, 2022 Vários estudos apontam que a expressão e a relação do ARHGAP26 na tumorigênese e progressão tumoral não são similares em diferentes tipos de tumores, sendo significamente diminuída na leucemia mielóide aguda e crônica, no câncer de ovário também (CHEN et al, 2019).…”

Section: Arhgap-26 -Proteína Ativadora De Rhoa Gtpase 26 E O Câncer G...unclassified

“…ARHGAP26 está localizado no interior da citomembrana, regulando a proliferação celular, apoptose a nível translacional (JARIUS et al, 2013, JING et al, 2022. Usualmente é expresso no citoplasma de células teciduais normais e em células tumorais, conforme observado em nosso estudo .…”

Section: Análise Da Fusão Gênica Cld18-arhgap26unclassified

Análise da fusão dos genes CLDN18-ARGHGAP26 no adenocarcinoma gástrico pós neodjuvância e sua correlação com expressão imuno-histoquímica das proteínas ARHGAP26, CLAUDINA 18, E-CADERINA em associação com aspectos clínicos-patológicos

Mariano

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Gastric cancer (GC) is an important cause of incidence and death worldwide, with adenocarcinoma (AG) being the most common type of gastric cancer. Molecular studies categorize them into four genomic subtypes: chromosomal instability, microsatellite instability, Epstein-Barr virus positive and genomically stable (GS). The GS subtype presents specific mutations, especially in the RHOA gene and the CLDN18-ARHGAP26 gene fusion, which result in impaired epithelial integrity, greater invasiveness of tumor cells, being more observed in diffuse AG. This is a case-control, retrospective and longitudinal study, based on the analysis of the CLDN18-ARHGAP26 gene fusion rate in correlation with an immunohistochemical study to evaluate the expression of the proteins Claudin 18, ARHGAP26 and E-cadherin in samples of gastric adenocarcinoma with and without neoadjuvant treatment, originating from gastrectomy surgical specimens performed between 2008 and 2017. For the molecular study, 78 frozen samples of AG were selected, stored in the Biorepository of the Digestive Surgery and Endoscopy Service of HCFMRP-USP, subjected to microtomy and evaluation of the percentage of tumor tissue represented in the samples. The immunohistochemical study of this same population was carried out using paraffin blocks archived at the Pathology Service of the Hospital das Clínicas of the Faculty of Medicine of Ribeirão Preto of the University of São Paulo. Forty-three frozen AG samples (11 neoadjuvants) exhibited good tumor representation for molecular study, with initial RNA extraction being performed, followed by amplification by RT-qPCR and DNA sequencing. No gene fusion pattern was detected. The immunohistochemical study to evaluate the expression of ARHGAP26 and E-cadherin proteins in AGs showed a preserved expression pattern in approximately 90% of GC cases. Decreased expression of the Claudin 18 protein was detected in 78% of cases, especially in intestinal-type cases (100%). A weak correlation was observed between ARHGAP26-CLDN18 proteins. No statistically significant association was observed between the immunohistochemical expressions of the proteins ARHGAP26, Claudin 18, E-cadherin and clinical variables (overall survival, diseasefree survival, histological type and clinical stage). No statistically significant association was detected between the types of treatment received by the patient and the immunohistochemical expressions of ARHGAP26, Claudin 18 and E-cadherin proteins. An association was observed between post-neoadjuvant tumor regression and immunohistochemical expressions of ARHGAP26 and E-cadherin proteins. Overall and disease-free survival times were longer in patients undergoing neoadjuvant treatment compared to adjuvant treatment. Our work highlights the importance of claudin 18 as a prognostic indicator related to disease progression in gastric adenocarcinoma and suggests its use in routine histopathological diagnostic methods, allowing to identify patients at risk for complementary molecular assessment and more specific targe...

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CLDN18-ARHGAP26 function in gastric cancer and be a new therapeutic target by ABCG2 and ABCB1 pathway

Cited by 3 publications

References 28 publications

Lactobacillus casei enhances the apoptosis inducing effect of geniposide on U87 human glioma cells in vitro

Lactobacillus casei enhances the apoptosis inducing effect of geniposide on U87 human glioma cells in vitro

Effects of Jiawei Huangqi Guizhi Decoction on the expression of GAS, MTL, GC, and TGF-β3 signaling pathways in CAG rats

Análise da fusão dos genes CLDN18-ARGHGAP26 no adenocarcinoma gástrico pós neodjuvância e sua correlação com expressão imuno-histoquímica das proteínas ARHGAP26, CLAUDINA 18, E-CADERINA em associação com aspectos clínicos-patológicos

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