ArticlePediatric surgery international2012
Apoptosis sensitizers enhance cytotoxicity in hepatoblastoma cells.
Article in Pediatric surgery international, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Review
- Obatoclax and Paclitaxel Synergistically Induce Apoptosis and Overcome Paclitaxel Resistance in Urothelial Cancer Cells.Cancers · 2018Article
- The role of BH3-mimetic drugs in the treatment of pediatric hepatoblastoma.International journal of molecular sciences · 2015Review
- Effect of duplex drugs linking 2'-deoxy-5-fluorouridine (5-FdU) with 3'-C-ethynylcytidine (ECyd) on hepatoblastoma cell lines.Pediatric surgery international · 2013Article
- Pharmacological inhibition of beta-catenin in hepatoblastoma cells.Pediatric surgery international · 2013Article
- Anti-cancer drug discovery and development: Bcl-2 family small molecule inhibitors.Communicative & integrative biology · 2012Article
- Understanding sensitivity to BH3 mimetics: ABT-737 as a case study to foresee the complexities of personalized medicine.Journal of molecular signaling · 2012Article
- In vitro evaluation of the Aurora kinase inhibitor VX-680 for Hepatoblastoma.Pediatric surgery international · 2012Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeDrug resistance remains a major challenge for the treatment of high-risk hepatoblastoma (HB). To enhance effectiveness of chemotherapy we modulate apoptosis in HB cells in vitro.
methodsViability was monitored in HB cells (HuH6, HepT1) and fibroblasts in monolayer and spheroid cultures treated with ABT-737, obatoclax, HA14-1, and TW-37 and each in combination with CDDP, etoposide, irinotecan, paclitaxel, and DOXO in a MTT assay. Western blot analyses were performed to determine expressions of pro- and anti-apoptotic proteins.
resultsObatoclax and ABT-737 led to a dose-dependent decrease of viability in HB cells at concentrations above 0.3 μM. TW-37 and HA14-1 were less effective. ABT-737 and obatoclax had additive effects when combined with CDDP, etoposide, irinotecan, paclitaxel, or DOXO. This was also observed for fibroblast, however, for higher drug concentrations. In spheroid cultures, relative expression of Bcl-XL was increased, Bax was decreased, Mcl-1 was low, and Bcl-2 was not detected compared to 2D cultures, denoting an anti-apoptotic state in spheroids. Obatoclax and ABT-737 have overcome the resistance to CDDP. HuH6 cells have shown higher susceptability for apoptosis sensitizers than HepT1.
conclusionThe data provide evidence that ABT-737 and obatoclax might improve treatment results in children with HB.
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