Related Experiment Video
Updated: Jun 29, 2025
Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Chemo-Senolytic Therapeutic Potential against Angiosarcoma
Xuebing Wang1, Claire Yik-Lok Chung1, Ai Yoshioka2
1Division of Genome Biology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan.
Abstract:
Angiosarcoma is an aggressive soft-tissue sarcoma with a poor prognosis. Chemotherapy for this cancer typically employs paclitaxel, a taxane (genotoxic drug), although it has a limited effect owing to chemoresistance to prolonged treatment. In this study, we examine an alternative angiosarcoma treatment approach that combines chemotherapeutic and senolytic agents. We find that the chemotherapeutic drugs cisplatin and paclitaxel efficiently induce senescence in angiosarcoma cells. Subsequent treatment with the senolytic agent ABT-263 eliminates senescent cells by activating the apoptotic pathway. In addition, expression analysis indicates that senescence-associated secretory phenotype genes are activated in senescent angiosarcoma cells and that ABT-263 treatment downregulates IFN-I pathway genes in senescent cells. Moreover, we show that cisplatin treatment alone requires high doses to remove angiosarcoma cells. In contrast, lower doses of cisplatin are sufficient to induce senescence, followed by the elimination of senescent cells by the senolytic treatment. This study sheds light on a potential therapeutic strategy against angiosarcoma by combining a relatively low dose of cisplatin with the ABT-263 senolytic agent, which can help ease the deleterious side effects of chemotherapy.
Insights
This study explores a new angiosarcoma treatment combining chemotherapy and senolytic agents. A low-dose cisplatin and ABT-263 combination effectively eliminates senescent cancer cells, potentially reducing chemotherapy side effects.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Angiosarcoma is an aggressive cancer with poor prognosis.
- Current chemotherapy with paclitaxel shows limited efficacy due to chemoresistance.
- There is a need for novel therapeutic strategies for angiosarcoma.
Purpose of the Study:
- To investigate a combination therapy for angiosarcoma using chemotherapeutic and senolytic agents.
- To evaluate the efficacy of cisplatin and paclitaxel in inducing senescence in angiosarcoma cells.
- To assess the senolytic agent ABT-263 in eliminating senescent angiosarcoma cells.
Main Methods:
- Induction of senescence in angiosarcoma cells using cisplatin and paclitaxel.
- Treatment of senescent cells with the senolytic agent ABT-263.
- Analysis of gene expression, including senescence-associated secretory phenotype (SASP) and IFN-I pathways.
- Dose-response assessment of cisplatin for angiosarcoma cell elimination.
Main Results:
- Cisplatin and paclitaxel effectively induce senescence in angiosarcoma cells.
- ABT-263 eliminates senescent angiosarcoma cells via apoptosis.
- Senescent cells exhibit activated SASP genes, which are downregulated by ABT-263.
- Lower doses of cisplatin combined with ABT-263 are sufficient for angiosarcoma cell elimination compared to high-dose cisplatin alone.
Conclusions:
- Combining low-dose cisplatin with the senolytic agent ABT-263 presents a promising therapeutic strategy for angiosarcoma.
- This combination approach may reduce the toxic side effects associated with conventional chemotherapy.
- Targeting senescent cells offers a novel avenue for angiosarcoma treatment.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:49Cancer Therapies
However, cancer treatments can pose several challenges, as therapies used to kill cancer cells are generally also toxic to normal cells. Moreover, cancer cells mutate rapidly and can develop resistance to chemical agents or radiation therapy. Besides, all types of cancer cells may not respond to the same therapy. Some cancer cells respond to one...
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...