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

2020 ◽  
Author(s):  
Min-Young Kim ◽  
Jung-Young Shin ◽  
Jeong-Oh Kim ◽  
Kyoung-Hwa Son ◽  
Yeon Sil Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Tumor Growth ◽  
Blood Vessels ◽  
Tumor Size ◽  
Tumor Necrosis ◽  
Ki 67 ◽  
Xenograft Mouse Model ◽  
Glut 1 ◽  
Term Administration

Abstract Background: To evaluate the anti-tumor efficacy of CKD-516 in combined with irradiation (IR) and examine tumor necrosis, delayed tumor growth, and expression of molecules involved in hypoxia and angiogenesis. Methods : A xenograft mouse model of lung cancer was established. The tumor was exposed to irradiation (IR) for 5 days per week. CKD-516 was administered with ​​two treatment schedules (day 1 or days 1 and 5) at one hour after IR. After the administration, tumor tissues were stained with hematoxylin and eosin and pimonidazole. HIF1 , Glut-1, VEGF, CD31 and Ki-67 expression were evaluated by Immunohistochemical staining. Results: With short-term administration, IR and CKD-516+IR (d1) significantly reduced tumor size ( p = 0.0062 and p = 0.0051, respectively). CKD-516+IR groups were remarkably reduced blood vessels ( p < 0.005). In particular, CKD-516+IR (d1) resulted in the most extensive tumor necrosis, which was significantly increased with large hypoxic area ( p = 0.02) and decreased HIF1 , Glut-1, VEGF, and Ki-67 expressions. Long-term administration of CKD-516+IR reduced tumor size 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 notably increased HIF1 expression ( p = 0.0047), but significantly diminished VEGF expression ( p = 0.0046). Conclusions : Taken together, our results demonstrate that CKD-516 in combination with IR can significantly enhance the anti-tumor efficacy compared to CKD-516 or IR alone in lung cancer xenograft mice.

scholarly journals Anti-tumor efficacy of CKD-516 in combination with radiation in xenograft lung cancer mouse model

2019 ◽  
Author(s):  
Min-Young Kim ◽  
Jung-Young Shin ◽  
Jeong-Oh Kim ◽  
Kyoung-Hwa Son ◽  
Chan-Kwon Jung ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Tumor Growth ◽  
Blood Vessels ◽  
Tumor Size ◽  
Tumor Necrosis ◽  
Ki 67 ◽  
Glut 1 ◽  
Term Administration ◽  
Xenograft Mice

Abstract Background: To evaluate the anti-tumor efficacy of CKD-516 in combined with irradiation (IR) and examine tumor necrosis, delayed tumor growth, and expression of molecules involved in hypoxia and angiogenesis. Methods : A xenograft mouse model of lung cancer was established. The tumor was exposed to irradiation (IR) for 5 days per week. CKD-516 was administered with ​​two treatment schedules (day 1 or days 1 and 5) at one hour after IR. After the administration, tumor tissues were stained with hematoxylin and eosin and pimonidazole. HIF1 , Glut-1, VEGF, CD31 and Ki-67 expression were evaluated by Immunohistochemical staining. Results: With short-term administration, IR and CKD-516+IR (d1) significantly reduced tumor size ( p = 0.0062 and p = 0.0051, respectively). CKD-516+IR groups were remarkably reduced blood vessels ( p < 0.005). In particular, CKD-516+IR (d1) resulted in the most extensive tumor necrosis, which was significantly increased with large hypoxic area ( p = 0.02) and decreased HIF1 , Glut-1, VEGF, and Ki-67 expressions. Long-term administration of CKD-516+IR reduced tumor size 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 notably increased HIF1 expression ( p = 0.0047), but significantly diminished VEGF expression ( p = 0.0046). Conclusion: Taken together, our results demonstrate that CKD-516 in combination with IR can significantly enhance the anti-tumor efficacy compared to CKD-516 or IR alone in lung cancer xenograft mice. Keywords: Irradiation, Tumor necrosis, Hypoxia, Squamous cell carcinoma of lung, Xenograft mice

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

2020 ◽  
Author(s):  
Min-Young Kim ◽  
Jung-Young Shin ◽  
Jeong-Oh Kim ◽  
Kyoung-Hwa Son ◽  
Yeon Sil Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Mouse Model ◽  
Tumor Growth ◽  
Blood Vessels ◽  
Tumor Necrosis ◽  
Tumor Volume ◽  
Lung Squamous Cell Carcinoma ◽  
Ki 67 ◽  
Glut 1

Abstract Background: Hypoxic tumors are known to be highly resistant to radiotherapy and cause poor prognosis in non-small-cell lung cancer (NSCLC) patients. Vascular disrupting agents (VDAs) mainly affect blood vessels located in the central area of the tumor and lead to a rapid decrease in blood, resulting in massive apoptotic tumor cell death. Thus, we evaluate the anti-tumor efficacy of CKD-516 in combination with irradiation (IR) and examine tumor necrosis, delayed tumor growth, and expression of proteins involved in hypoxia and angiogenesis in this study.Methods: A 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 the treatment, tumor tissues were stained with hematoxylin and eosin and pimonidazole. HIF-1α, Glut-1, VEGF, CD31, and Ki-67 expression levels were evaluated by immunohistochemical staining.Results: Short-term treatment with IR alone and CKD-516+IR (d1) significantly reduced tumor volume (p = 0.006 and p = 0.048, respectively). Treatment with CKD-516+IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p < 0.005). More specifically, CKD-516+IR (d1) caused the most extensive tumor necrosis, which resulted in a significantly large hypoxic area (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).Conclusions: Taken 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.

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

2020 ◽  
Author(s):  
Min-Young Kim ◽  
Jung-Young Shin ◽  
Jeong-Oh Kim ◽  
Kyoung-Hwa Son ◽  
Yeon Sil Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Mouse Model ◽  
Tumor Growth ◽  
Blood Vessels ◽  
Tumor Necrosis ◽  
Tumor Volume ◽  
Lung Squamous Cell Carcinoma ◽  
Ki 67 ◽  
Glut 1

Abstract Background: Hypoxic 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 massive apoptotic 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.Methods: A 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.Results: Short-term treatment with IR alone and CKD-516+IR (d1) significantly reduced tumor volume (p = 0.006 and p = 0.048, respectively). Treatment with CKD-516+IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p < 0.005). More specifically, CKD-516+IR (d1) caused the most extensive tumor necrosis, which resulted in a significantly large hypoxic area (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).Conclusions: Taken 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.

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

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Min-Young Kim ◽  
Jung-Young Shin ◽  
Jeong-Oh Kim ◽  
Kyoung-Hwa Son ◽  
Yeon Sil Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Mouse Model ◽  
Tumor Growth ◽  
Blood Vessels ◽  
Tumor Necrosis ◽  
Tumor Volume ◽  
Lung Squamous Cell Carcinoma ◽  
Ki 67 ◽  
Glut 1

Abstract Background Hypoxic 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. Methods A 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. Results Short-term treatment with IR alone and CKD-516 + IR (d1) significantly reduced tumor volume (p = 0.006 and p = 0.048, respectively). Treatment with CKD-516 + IR (d1 and d1, 5) resulted in a marked reduction in the number of blood vessels (p < 0.005). More specifically, CKD-516 + IR (d1) caused the most extensive tumor necrosis, which resulted in a significantly large hypoxic area (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). Conclusions Taken 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.

scholarly journals Thymoquinone Inhibits Tumor Growth and Induces Apoptosis in a Breast Cancer Xenograft Mouse Model: The Role of p38 MAPK and ROS

PLoS ONE ◽  
2013 ◽  
Vol 8 (10) ◽  
pp. e75356 ◽  
Author(s):  
Chern Chiuh Woo ◽  
Annie Hsu ◽  
Alan Prem Kumar ◽  
Gautam Sethi ◽  
Kwong Huat Benny Tan
Keyword(s):  
Breast Cancer ◽  
Mouse Model ◽  
Tumor Growth ◽  
P38 Mapk ◽  
Xenograft Mouse Model ◽  
Breast Cancer Xenograft

scholarly journals α-Hederin Inhibits the Growth of Lung Cancer A549 Cells in vitro and in vivo by Increasing SIRT6 Dependent Glycolysis

2020 ◽  
Author(s):  
cong fang ◽  
Yahui Liu ◽  
Lanying Chen ◽  
Yingying Luo ◽  
Yaru Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mouse Model ◽  
Protein Expression ◽  
Glucose Uptake ◽  
A549 Cells ◽  
Lactate Production ◽  
Tumor Xenograft ◽  
Xenograft Mouse Model ◽  
Atp Generation

Abstract Background: α-hederin an effective component of Pulsatilla chinensis (Bunge) Regel, Studies showed that α-hederin exert many pharmacological activities, However, the effect of α-hederin on metabolism is still unclear. This study aimed to illuminate the role of α-hederin in glucose metabolism in lung cancer cells and investigate the molecular mechanism of α-hederin. Methods: CCK8 and colony formation assays were employed to assess the anti-proliferative effects induced by α-hederin. Glucose uptake, ATP generation, and reduced lactate production were measured using kits, and an A549 tumor xenograft mouse model of lung cancer was used to assess the in vivo antitumor effect of α-hederin (5, 10 mg/kg). Glycolytic-related key enzymes hexokinase 2 (HK2), glucose transporters 1 (GLUT1), pyruvate kinase M2 (PKM2), lactate dehydrogenase A (LDHA), monocarboxylate transporter (MCT4), c-Myc, Hypoxia inducible factor-1α (HIF-1α) and Sirtuin 6 (SIRT6) protein expression were detected by western blotting and immunohistochemical staining and SIRT6 inhibitors was verified in A549 cells. Results: Our results showed that cell proliferation was significantly inhibited by α-hederin in a dose-dependent manner and that α-hederin inhibited glucose uptake and ATP generation and reduced lactate production. Furthermore, α-hederin remarkably inhibited HK2, GLUT1, PKM2, LDHA, MCT4, c-Myc, HIF-1α and activated SIRT6 protein expression. Using inhibitors, we proved that α-hederin inhibits glycolysis by activating SIRT6. Moreover, a tumor xenograft mouse model of lung cancer further confirmed that α-hederin inhibits lung cancer growth via inhibiting glycolysis in vivo. Conclusions: α-hederin inhibits the growth of non-small cell lung cancer A549 cells by inhibiting glycolysis. The mechanism of glycolysis inhibition includes α-hederin activating the expression of the glycolytic related protein SIRT6.

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