The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes

Šeborová, Karolína; Kloudova-Spalenkova, Alzbeta; Koucká, Kamila; Holý, Petr; Ehrlichová, Marie; Wang, Changwei; Ojima, Iwao; Voleska, Iveta; Daniel, Petr; Balušíková, Kamila; Jelínek, Michael; Kovář, Jan; Rob, Lukáš; Hruda, Martin; Mrhalová, Marcela; Souček, Pavel; Václavíková, Radka

doi:10.3390/ijms23010073

Cited by 9 publications

(8 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The combined regimen composed of PTX with both third generation taxanes, used in the present study, caused downregulation of CPS1 in the PTX-resistant NCI/ADR-RES-derived mouse xenograft model in vivo . Furthermore, CPS1 overexpression was also associated with poor survival of patients with epithelial ovarian carcinoma ( Seborova et al, 2022 ). We therefore assume that a detailed study of effects of taxanes and their combinations on the gene expression profile (and potentially also epigenetic factors) may help decipher not only the mechanisms behind their antitumor activity, but also reveal new candidate biomarkers and/or targets enabling personalized therapy of solid tumors.…”

Section: Discussionmentioning

confidence: 99%

Anticancer regimens containing third generation taxanes SB-T-121605 and SB-T-121606 are highly effective in resistant ovarian carcinoma model

et al. 2022

Self Cite

View full text Add to dashboard Cite

Taxanes are widely used in the treatment of ovarian carcinomas. One of the main problems with conventional taxanes is the risk of development of multidrug resistance. New-generation synthetic experimental taxoids (Stony Brook Taxanes; SB-T) have shown promising effects against various resistant tumor models. The aim of our study was to compare the in vitro efficacy, intracellular content, and in vivo antitumor effect of clinically used paclitaxel (PTX) and SB-Ts from the previously tested second (SB-T-1214, SB-T-1216) and the newly synthesized third (SB-T-121402, SB-T-121605, and SB-T-121606) generation in PTX resistant ovarian carcinoma cells NCI/ADR-RES. The efficacy of the new SB-Ts was up to 50-times higher compared to PTX in NCI/ADR-RES cells in vitro. SB-T-121605 and SB-T-121606 induced cell cycle arrest in the G2/M phase much more effectively and their intracellular content was 10–15-times higher, when compared to PTX. Incorporation of SB-T-121605 and SB-T-121606 into therapeutic regimens containing PTX were effective in suppressing tumor growth in vivo in NCI/ADR-RES based mice xenografts at small doses (≤3 mg/kg), where their adverse effects were eliminated. In conclusion, new SB-T-121605 and SB-T-121606 analogs are promising candidates for the next phase of preclinical testing of their combination therapy with conventional taxanes in resistant ovarian carcinomas.

show abstract

Section: Discussionmentioning

confidence: 99%

Anticancer regimens containing third generation taxanes SB-T-121605 and SB-T-121606 are highly effective in resistant ovarian carcinoma model

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…This could be due to the differences in the mechanism of action of both therapies. On one hand, in CT, PX must reach the cell cytoplasm to exert its stabilizing effect on microtubules [ 67 , 68 ], so it can be extruded by ABCG2 proteins [ 69 , 70 ] or metabolized by CYP proteins [ 65 ]. On the other hand, when PX and Carb are administered in a metronomic scheme, they exert a pro-apoptotic effect by the activation of mAchRs, which are present in the cell membrane [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

Hexachlorobenzene as a differential modulator of the conventional and metronomic chemotherapy response in triple negative breast cancer cells

Sanchez,

Vasquez Callejas,

Miret

et al. 2024

Exploration of Targeted Anti-Tumor Therapy

View full text Add to dashboard Cite

Aim: Triple negative breast cancer (TNBC) is usually treated with high doses of paclitaxel, whose effectiveness may be modulated by the action of environmental contaminants such as hexachlorobenzene. High doses of paclitaxel cause adverse effects such as low cellular selectivity and the generation of resistance to treatment due to an increase in the expression of multidrug resistance proteins (MRPs). These effects can be reduced using a metronomic administration scheme with low doses. This study aimed to investigate whether hexachlorobenzene modulates the response of cells to conventional chemotherapy with paclitaxel or metronomic chemotherapy with paclitaxel plus carbachol, as well as to study the participation of the MRP ATP-binding cassette transporter G2 (ABCG2) in human TNBC MDA-MB231 cells. Methods: Cells were treated with hexachlorobenzene alone or in combination with conventional or metronomic chemotherapies. The effects of treatments on cell viability were determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and the nuclear factor kappa B pathway participation was evaluated using a selective inhibitor. ABCG2 expression and its modulation were determined by western blot. Results: Results confirmed that paclitaxel reduces MDA-MB231 cell viability in a concentration-dependent manner. Results also showed that both conventional and metronomic chemotherapies reduced cell viability with similar efficacy. Although hexachlorobenzene did not modify cell viability per se, it did reverse the effect induced by the conventional chemotherapy, without affecting the efficacy of the metronomic chemotherapy. Additionally, a differential modulation of ABCG2 expression was determined, mediated by the nuclear factor kappa B pathway, which was directly related to the modulation of cell sensitivity to another cycle of paclitaxel treatment. Conclusions: The findings indicate that, in human TNBC MDA-MB231 cells, in the presence of hexachlorobenzene, the metronomic combination of paclitaxel plus carbachol is more effective in affecting the tumor biology than the conventional therapeutic administration scheme of paclitaxel.

show abstract

“…CPS1 (Carbamoyl-Phosphate Synthase 1) encodes a crucial mitochondrial enzyme that catalyzes the synthesis of carbamoyl phosphate in the urea cycle. Several recent studies showed the associations of CPS1 with some cancers such as gastric cancer and ovarian cancer [ 73 , 74 ]. Two recent published studies showed that the expression level of CPS1 was upregulated in LUAD tissue, and its high expression resulted in a poor survival rate [ 75 , 76 ].…”

Section: Discussionmentioning

confidence: 99%

A robust six-gene prognostic signature based on two prognostic subtypes constructed by chromatin regulators is correlated with immunological features and therapeutic response in lung adenocarcinoma

Chen,

Zhao,

2023

Aging

View full text Add to dashboard Cite

Accumulating evidence has demonstrated that chromatin regulators (CRs) regulate immune cell infiltration and are correlated with prognoses of patients in some cancers. However, the immunological and prognostic roles of CRs in lung adenocarcinoma (LUAD) are still unclear. Here, we systematically revealed the correlations of CRs with immunological features and the survival in LUAD patients based on a cohort of gene expression datasets from the public TCGA and GEO databases and real RNA-seq data by an integrative analysis using a comprehensive bioinformatics method. Totals of 160 differentially expressed CRs (DECRs) were identified between LUAD and normal lung tissues, and two molecular prognostic subtypes (MPSs) were constructed and evaluated based on 27 prognostic DECRs using five independent datasets ( p =0.016, <0.0001, =0.008, =0.00038 and =0.00055, respectively). Six differentially expressed genes (DEGs) ( CENPK , ANGPTL4 , CCL20 , CPS1 , GJB3 , TPSB2 ) between two MPSs had the most important prognostic feature and a six-gene prognostic model was established. LUAD patients in the low-risk subgroup showed a higher overall survival (OS) rate than those in the high-risk subgroup in nine independent datasets ( p <0.0001, =0.021, =0.016, =0.0099, <0.0001, =0.0045, <0.0001, =0.0038 and =0.00013, respectively). Six-gene prognostic signature had the highest concordance index of 0.673 compared with 19 reported prognostic signatures. The risk score was significantly correlated with immunological features and activities of oncogenic signaling pathways. LUAD patients in the low-risk subgroup benefited more from immunotherapy and were less sensitive to conventional chemotherapy agents. This study provides novel insights into the prognostic and immunological roles of CRs in LUAD.

show abstract

The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes

Cited by 9 publications

References 66 publications

Anticancer regimens containing third generation taxanes SB-T-121605 and SB-T-121606 are highly effective in resistant ovarian carcinoma model

Anticancer regimens containing third generation taxanes SB-T-121605 and SB-T-121606 are highly effective in resistant ovarian carcinoma model

Hexachlorobenzene as a differential modulator of the conventional and metronomic chemotherapy response in triple negative breast cancer cells

A robust six-gene prognostic signature based on two prognostic subtypes constructed by chromatin regulators is correlated with immunological features and therapeutic response in lung adenocarcinoma

Contact Info

Product

Resources

About