Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Combination effects of capecitabine, irinotecan and 17-AAG on colorectal cancer cell line (HT-29)

ABSTRACT:

Objevtive

Evasion of apoptosis is a major feature of cancer cells, therefore designing treatment strategies to target apoptotic pathways seems effective. In this study, we investigate the effect of 17-AAG (17-allylaminogeldanamycin) alone and in double and triple combination with capecitabine (Cap) and irinotecan (IR) on HT-29 colon cancer cell line apoptosis.

Methods

Capase-3, 8, 9, p53 and NF-κB genes expression were analyzed by Real-time PCR. DNA laddering assay was performed to confirm Real-time PCR results.

Results

Our results showed that all single treatment groups elevated expression of caspase-3, 8, and 9 significantly and IR/Cap was the only double combination group that could upregulate caspase-8 and -9. NF-κB was down-regulated in single treatment and IR/Cap double combination group, significantly. 17-AAG mono-treatment and IR/Cap and Cap/17-AAG double combination group significantly upregulated p53 gene expression.

Conclusion

Our findings showed proapoptotic effects of 17-AAG alone and in combination with Cap and IR. These findings propose 17-AAG in combination with routine chemotherapy, as a new protocol for colorectal cancer combination therapy. Highlights • Targeted therapy of apoptosis is the main effective way against of cancer cells.• 17-AAG alone and in combination with Cap and IR can regulate the pro-apoptotic factors.• Combination therapy has more effective than single therapy.

SUBMITTER: Zeynali-Moghaddam S

PROVIDER: S-EPMC9207062 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Barcode Sequencing Data of Capecitabine Resistant Caco-2 and Irinotecan Resistant HT-29 Cell Lines

Project description:Caco-2 and HT-29 cells were barcoded using the CloneTracker lentiviral barcode library and then irinotecan and capecitabine resistant derivatives of these cell lines were established. Four million barcoded Caco-2 and HT-29 cell were seeded into 15 cm cell culture dishes. When the cells reached confluency, two million cells per dish were seeded into four different 15 cm dishes with 25 mL medium (DMSO Control, Replica A, B, C) and two million cell pellets were stocked as initial cell population.For Caco-2 cell line, mediums in the dishes were changed twice a week with fresh mediums containing IC50 dose (4 months) and subsequently 2x IC50 dose (2 months) of capecitabine, for HT-29 cell line IC50 dose (6 months) of irinotecan. Caco-2 and HT-29 cell lines treated with DMSO were given the same amount of DMSO used in dissolving compounds as fresh medium. Following the end points of six months for each cell line, DNA isolation from harvested cell lines and collected medium of resistant B cell lines were carried out and barcodes were sequenced.

2023-07-11 | E-MTAB-12818 | biostudies-arrayexpress

Bevacizumab in combination with biweekly capecitabine and irinotecan, as first-line treatment for patients with metastatic colorectal cancer.

Project description:Combination of capecitabine and irinotecan (XELIRI regimen) is an active and well tolerated treatment for metastatic colorectal cancer (mCRC). The aim of this study was to evaluate the efficacy and safety of this regimen in combination with bevacizumab (BV), as first-line treatment for mCRC.A total of 46 consecutive patients received a combination of BV (5 mg kg⁻¹, day 1), irinotecan (175 mg m⁻², day 1) and capecitabine (1000 mg m⁻² twice daily on day 2-8), every 2 weeks. Patients were treated until disease progression or unacceptable toxicity. The primary objective was to determine the progression-free survival (PFS) and safety profile.The overall response rate (ORR) was 67.4%, with a disease control rate (ORR+stable disease) of 93.5%. Median PFS and overall survival (OS) were 12.3 months (95% confidence interval (CI): 6.5-18.1 months) and 23.7 months (95% CI: 16.7-30.6 months), respectively. The most frequent grade 3/4 treatment-related adverse events were asthenia (7%), diarrhoea (7%), nausea (9%) and vomiting (7%).Bevacizumab combined with biweekly XELIRI is a highly active first-line regimen for mCRC treatment, showing encouraging PFS, ORR and OS with a good tolerability.

| S-EPMC2990572 | biostudies-other

Phase I/II trial of capecitabine, oxaliplatin, and irinotecan in combination with bevacizumab in first line treatment of metastatic colorectal cancer.

Project description:Phase III studies have demonstrated the efficacy of FOLFOXIRI regimens (5-fluorouracil/leucovorin, oxaliplatin, irinotecan) with/without bevacizumab in metastatic colorectal cancer (mCRC). Capecitabine is an orally administered fluoropyrimidine that may be used instead of 5-fluorouracil/leucovorin. We evaluated a triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab in 53 patients with mCRC. A Phase I study identified the maximum tolerated dose of irinotecan as 150 mg/m². Median follow-up in a subsequent Phase II study using this dose was 28 months (74% progressed). For all patients, a complete response was achieved in 4% and a partial response in 60%; median progression-free survival (PFS) was 16 months and median overall survival (OS) was 28 months. Median PFS was longer for patients with an early treatment response (28 vs. 9 months for others; P = 0.024), or early tumor shrinkage (25 vs. 9 months for others; P = 0.006), or for patients suitable for surgical removal of metastases with curative intent (median not reached vs. 9 months for others; P = 0.001). Median OS was longer for patients with early tumor shrinkage (median not reached vs. 22 months for others; P = 0.006) or surgery (median not reached vs. 22 months for others, P = 0.002). K-ras mutations status did not influence PFS (P = 0.88) or OS (P = 0.82). Considerable Grade 3/4 toxicity was encountered (36% for diarrhea, 21% for vomiting and 17% for fatigue). In conclusion, the 3-weekly triple-chemotherapy regimen of capecitabine, oxaliplatin, and irinotecan, plus bevacizumab, was active in the first-line treatment of mCRC, although at the expense of a high level of toxicity.

| S-EPMC4618621 | biostudies-literature

Aberrant Cosmc genes result in Tn antigen expression in human colorectal carcinoma cell line HT-29.

Project description:The Tn antigen, which arises from mutation in the Cosmc gene is one of the most common tumor associated carbohydrate antigens. Cosmc resides in X24 encoded by a single gene and functions as a specific molecular chaperone for T-synthase. While the Tn antigen cannot be detected in normal cells, Cosmc mutations inactivate T-synthase and consequently result in Tn antigen expression within certain cancers. In addition to this Cosmc mutation-induced expression, the Tn antigen is also expressed in such cell lines as Jurkat T, LSC and LS174T. Whether the Cosmc mutation is present in the colon cancer cell line HT-29 is still unclear. Here, we isolate HT-29-Tn+ cells from HT-29 cells derived from a female colon cancer patient. These HT-29-Tn+ cells show a loss of the Cosmc gene coding sequence (CDS) leading to an absence of T-synthase activity and Tn antigen expression. Additionally, almost no methylation of Cosmc CpG islands was detected in HT-29-Tn+ as well as in HT-29-Tn- and Tn- tumor cells from male patients. In contrast, the methylation frequency of CpG island of Cosmc in normal female cells was ~50%. Only one active allele of Cosmc existed in HT-29-Tn+ and HT-29-Tn- cells as based upon detection of SNP sites. These results indicate that Tn antigens expression and T-synthase inactivity in HT-29-Tn+ cells can be related to the absence of CDS in Cosmc active alleles, while an inactive allele deletion of Cosmc in HT-29 cells has no influence on Cosmc function.

| S-EPMC4440074 | biostudies-literature

Knockdown of KLK12 inhibits viability and induces apoptosis in human colorectal cancer HT-29 cell line.

Project description:Kallikrein‑related peptidase 12 (KLK12) is overexpressed in cancer tissues including gastric, breast and prostate cancer. However, the role of KLK12 in colorectal cancer is not fully understood. In the present study, the level of KLK12 was determined by performing reverse transcription‑polymerase chain reaction (RT‑qPCR) in colorectal cancer tissues and cell lines. Lipofectamine® 2000 was used to transfect HT‑29 cells to overexpress and knockdown KLK12. Cell viability, migration, invasion and apoptosis were detected by MTT, wound healing, Transwell and flow cytometry assays, respectively. The mRNA and protein expression levels of EMT‑associated proteins, apoptosis‑associated proteins, phosphorylated adenosine monophosphate‑activated protein kinase (p‑AMPK) and phosphorylated mammalian target of rapamycin (p‑mTOR) were determined by RT‑qPCR and western blot analysis. It was identified that the KLK12 mRNA levels were increased significantly in colorectal cancer tissues and cell lines. KLK12 small interfering RNA inhibited cell viability, migration and invasion. Furthermore, epithelial‑mesenchymal transition (EMT)‑associated proteins were altered by siKLK12. Cell apoptosis was induced by KLK12 downregulation, which was demonstrated by the changes in apoptosis‑associated proteins; however, KLK12 overexpression produced the opposite effect. SiKLK12 enhanced the expression of p‑AMPK and suppressed the expression of p‑mTOR, while KLK12 overexpression had the opposite effect. Promotion of KLK12 overexpression‑induced cell viability was reversed by 5‑aminoimidazole‑4‑carboxamide ribonucleotide, an activator of the AMPK signaling pathway, and rapamycin, a specific inhibitor of the mTOR signaling pathway. Taken together, the results of the present study indicated that KLK12 was overexpressed in colorectal cancer and may regulate cell behavior, potentially via the AMPK and mTOR pathways.

| S-EPMC6777684 | biostudies-literature

Effect of sodium butyrate on colorectal cancer cell line HT-29

Project description:Analysis of colorectal cancer (CRC) cell line HT-29 treated with Sodium Butyrate. Sodium Butyrate, a HDAC inhibitor present in gut, can differentiate the undifferentiated HT-29 to enterocytes by the induction of brush border enzyme alkaline phosphatase. Results provide the transcriptional profiling underlying the butyrate-induced differentiation of CRC.

2016-12-31 | GSE61429 | GEO

Expression data from human HT-29 immortalized colorectal adenocarcinoma cell line

Project description:Gene expression profiling for identification of genes regulated by DNA methylation

2012-01-01 | GSE29060 | GEO

Investigation of health benefits of cocoa in human colorectal cancer cell line, HT-29 through interactome analysis.

Project description:AimThis bioinformatics study aims to identify the potential key genes influenced by cocoa extraction treatment on colon cancer cell line HT-29 after 24h.BackgroundCocoa consumption has been claimed to have beneficial effects on human body including protection against diseases such as different types of cancers. However, the mechanisms behind this is still remained to be studied.MethodsThe microarray dataset (GSE94154) from GEO, was the source for differentially expressed genes (DEGs) extraction through GEO2R analysis. The comparison was between 3 controls of colorectal cell line HT-29 and 3 ones incubated with 500 µg cocoa extraction after 24 h. Afterwards, the top significant DEGs were assigned for protein-protein interaction network construction and analysis by Cytoscape v 3.7.0. and the related applications.ResultsThe findings indicate that there are 222 up-regulated and 28 down-regulated genes among 250 top-ranked DEGs in cocoa incubated group. What is more, centrality analysis of the DEGs network identified 10 hub-bottlenecks that ISG15, MX 1, and STAT1 were among the significant differential expression genes with the contribution in type 1 interferon signaling pathway, positive regulation of erythrocyte differentiation, and negative regulation of viral genome replication.ConclusionIn conclusion, the underlying mechanisms of cocoa treatment could be clarified by its up-regulatory and modulatory effect on prominent genes of tumor suppressor family. In other words, valuable clues for future clinical studies of cocoa health benefits are highlighted as anticancer agent in this study once validation studies are carried out.

| S-EPMC6441487 | biostudies-literature

Expression data from human HT-29 immortalized colorectal adenocarcinoma cell line

Project description:Gene expression profiling for identification of genes regulated by DNA methylation Total RNA was extracted from HT-29 cell line was hybridized on Affymetrix HGU133 Plus 2.0 microarrays

2012-01-01 | E-GEOD-29060 | biostudies-arrayexpress

Expression data from 17-AAG resistance cell line

Project description:Develop the 17-AAG resistance human lung cancer cell line and used microarrays to observe the gene alternnation

2017-01-11 | GSE93384 | GEO