Back to Search
Start Over
Lambda-Carrageenan Enhances the Effects of Radiation Therapy in Cancer Treatment by Suppressing Cancer Cell Invasion and Metastasis through Racgap1 Inhibition
- Source :
- Cancers, Vol 11, Iss 8, p 1192 (2019), Cancers, Volume 11, Issue 8
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- Radiotherapy is used extensively in cancer treatment, but radioresistance and the metastatic potential of cancer cells that survive radiation remain critical issues. There is a need for novel treatments to improve radiotherapy. Here, we evaluated the therapeutic benefit of &lambda<br />carrageenan (CGN) to enhance the efficacy of radiation treatment and investigated the underlying molecular mechanism. CGN treatment decreased viability in irradiated cancer cells and enhanced reactive oxygen species accumulation, apoptosis, and polyploid formation. Additionally, CGN suppressed radiation-induced chemoinvasion and invasive growth in 3D lrECM culture. We also screened target molecules using a gene expression microarray analysis and focused on Rac GTPase-activating protein 1 (RacGAP1). Protein expression of RacGAP1 was upregulated in several cancer cell lines after radiation, which was significantly suppressed by CGN treatment. Knockdown of RacGAP1 decreased cell viability and invasiveness after radiation. Overexpression of RacGAP1 partially rescued CGN cytotoxicity. In a mouse xenograft model, local irradiation followed by CGN treatment significantly decreased tumor growth and lung metastasis compared to either treatment alone. Taken together, these results suggest that CGN may enhance the effectiveness of radiation in cancer therapy by decreasing cancer cell viability and suppressing both radiation-induced invasive activity and distal metastasis through downregulating RacGAP1 expression.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_treatment
lcsh:RC254-282
Article
Metastasis
03 medical and health sciences
0302 clinical medicine
Radioresistance
medicine
metastasis
Viability assay
Cytotoxicity
radiotherapy
Gene knockdown
Chemistry
medicine.disease
invasion
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RacGAP1
Radiation therapy
030104 developmental biology
Oncology
Apoptosis
030220 oncology & carcinogenesis
Cancer cell
Cancer research
carrageenan
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Volume :
- 11
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....d623229a0d18e03cbd839e74a6d8d4a4