Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft mouse model of lung squamous cell carcinoma

Autor: Kyoung-Hwa Son, Jeong-Oh Kim, Chan Kwon Jung, Min Young Kim, Yeon Sil Kim, Jung-Young Shin, Jin-Hyoung Kang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
CD31
Male
Vascular Endothelial Growth Factor A
Cancer Research
Lung Neoplasms
Angiogenesis
Xenograft model
H&E stain
lcsh:RC254-282
Drug Administration Schedule
03 medical and health sciences
Benzophenones
Mice
0302 clinical medicine
Carcinoma
Non-Small-Cell Lung
Cell Line
Tumor
Vascular disrupting agent
Genetics
medicine
Pimonidazole
Animals
Humans
Lung cancer
Glucose Transporter Type 1
Tumor hypoxia
Radiotherapy
business.industry
Tumor necrosis
Valine
Squamous cell carcinoma of lung
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Hypoxia-Inducible Factor 1
alpha Subunit
Gene Expression Regulation
Neoplastic
Platelet Endothelial Cell Adhesion Molecule-1
030104 developmental biology
Ki-67 Antigen
Treatment Outcome
Oncology
030220 oncology & carcinogenesis
Cancer research
Immunohistochemistry
Tumor necrosis factor alpha
Irradiation
Dose Fractionation
Radiation
business
Research Article
Zdroj: BMC Cancer
BMC Cancer, Vol 20, Iss 1, Pp 1-14 (2020)
ISSN: 1471-2407
Popis: BackgroundHypoxic tumors are known to be highly resistant to radiotherapy and cause poor prognosis in non-small cell lung cancer (NSCLC) patients. CKD-516, a novel vascular disrupting agent (VDA), mainly affects blood vessels in the central area of the tumor and blocks tubulin polymerization, thereby destroying the aberrant tumor vasculature with a rapid decrease in blood, resulting in rapid tumor cell death. Therefore, we evaluated the anti-tumor efficacy of CKD-516 in combination with irradiation (IR) and examined tumor necrosis, delayed tumor growth, and expression of proteins involved in hypoxia and angiogenesis in this study.MethodsA xenograft mouse model of lung squamous cell carcinoma was established, and the tumor was exposed to IR 5 days per week. CKD-516 was administered with two treatment schedules (day 1 or days 1 and 5) 1 h after IR. After treatment, tumor tissues were stained with hematoxylin and eosin, and pimonidazole. HIF-1α, Glut-1, VEGF, CD31, and Ki-67 expression levels were evaluated using immunohistochemical staining.ResultsShort-term treatment with IR alone and CKD-516 + IR (d1) significantly reduced tumor volume (p = 0.006 andp = 0.048, respectively). Treatment with CKD-516 + IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p p = 0.02) and decreased HIF-1α, Glut-1, VEGF, and Ki-67 expression. Long-term administration of CKD-516 + IR reduced tumor volume and delayed tumor growth. This combination also greatly reduced the number of blood vessels (p = 0.0006) and significantly enhanced tumor necrosis (p = 0.004). CKD-516 + IR significantly increased HIF-1α expression (p = 0.0047), but significantly reduced VEGF expression (p = 0.0046).ConclusionsTaken together, our data show that when used in combination, CKD-516 and IR can significantly enhance anti-tumor efficacy compared to monotherapy in lung cancer xenograft mice.
Databáze: OpenAIRE
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