Effects of cediranib on proliferation, migration and invasion of liver cancer cells by inhibiting HIF-1α/VEGF pathway_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 HAN Zhiwei , ZHANG Dezhi , ZHAO Yupeng

Department of General Surgery, General Hospital of Yima Coal Industry Group Co., Ltd., Yima, Henan 472300, P. R. China;

Corresponding author：

HAN Zhiwei, Email: hweip1976@163.com

Keywords：

cediranib; hypoxia-inducible factor-1α/vascular endothelial growth factor pathway; liver cancer; cell proliferation; cell invasion

DOI：

10.7507/1007-9424.202106004

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To investigate the effects of cediranib on hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathway and proliferation, migration and invasion of liver cancer cells. Methods The hypoxia microenvironment was simulated in vitro, and different doses of cediranib were used to intervene the human hepatoma cell HepG2, MTT assay was used to detect the proliferation of human hepatoma cell HepG2, Transwell chamber assay was used to detect the invasion and migration of human hepatoma cell HepG2, tumor formation in nude mice was used to detect the growth of human hepatoma cell HepG2 in vivo, the angiogenesis of tumor tissue and expression level of HIF-1α/VEGF pathway protein were detected by immunohistochemistry. Results Compared with the control group, the proliferation rate, invasion and migration abilities, and the expression of HIF-1α/VEGF pathway proteins of human hepatoma cell HepG2 were significantly decreased in the different concentration of cediranib treatment group (P<0.05), the tumor volume and microvessel formation of tumor tissues in nude mice were significantly reduced (P<0.05). Conclusion Cediranib may inhibit the proliferation, migration and invasion of liver cancer cells by inhibiting HIF-1α/VEGF signaling pathway.

Citation： HAN Zhiwei, ZHANG Dezhi, ZHAO Yupeng. Effects of cediranib on proliferation, migration and invasion of liver cancer cells by inhibiting HIF-1α/VEGF pathway. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2022, 29(2): 167-172. doi: 10.7507/1007-9424.202106004 Copy

1.	Zhu H, Zhang S. Hypoxia inducible factor-1α/vascular endothelial growth factor signaling activation correlates with response to radiotherapy and its inhibition reduces hypoxia-induced angiogenesis in lung cancer. J Cell Biochem, 2018, 119(9): 7707-7718.
2.	Zhang B, Li YL, Zhao JL, et al. Hypoxia-inducible factor-1 promotes cancer progression through activating AKT/Cyclin D1 signaling pathway in osteosarcoma. Biomed Pharmacother, 2018, 105: 1-9.
3.	Li M, Xie H, Liu Y, et al. Knockdown of hypoxia-inducible factor-1 alpha by tumor targeted delivery of CRISPR/Cas9 system suppressed the metastasis of pancreatic cancer. J Control Release, 2019, 304: 204-215.
4.	Koyasu S, Kobayashi M, Goto Y, et al. Regulatory mechanisms of hypoxia-inducible factor 1 activity: two decades of knowledge. Cancer Sci, 2018, 109(3): 560-571.
5.	Park SA, Jeong MS, Ha KT, et al. Structure and function of vascular endothelial growth factor and its receptor system. BMB Rep, 2018, 51(2): 73-78.
6.	Lenz N, Hirschburger M, Roehrig R, et al. Application of continuous wound-infusion catheters in lung transplantation: a retrospective data analysis. Thorac Cardiovasc Surg, 2017, 65(5): 403-409.
7.	Kouvaras E, Christoni Z, Siasios I, et al. Hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in cartilage tumors. Biotech Histochem, 2019, 94(4): 283-289.
8.	Tang E, Wang Y, Liu T, et al. Gastrin promotes angiogenesis by activating HIF-1α/β-catenin/VEGF signaling in gastric cancer. Gene, 2019, 704: 42-48.
9.	Orbegoso C, Marquina G, George A, et al. The role of cediranib in ovarian cancer. Expert Opin Pharmacother, 2017, 18(15): 1637-1648.
10.	Shen S, Luo X, Gao K, et al. Identification and integrative analysis of microRNAs and mRNAs involved in proliferation and invasion of pressure-treated human liver cancer cell lines. Mol Med Rep, 2019, 20(1): 375-387.
11.	Liu K, Tian T, Zheng Y, et al. Scutellarin inhibits proliferation and invasion of hepatocellular carcinoma cells via down-regulation of JAK2/STAT3 pathway. J Cell Mol Med, 2019, 23(4): 3040-3044.
12.	Momeny M, Sankanian G, Hamzehlou S, et al. Cediranib, an inhibitor of vascular endothelial growth factor receptor kinases, inhibits proliferation and invasion of prostate adenocarcinoma cells. Eur J Pharmacol, 2020, 882: 173298. doi: 10.1016/j.ejphar.2020.173298.
13.	Morikawa N, Nilsson MB, Guijarro I, et al. Evaluation of the combination of olaparib and cediranib in small-cell lung cancer cells. Cancer Res, 2018, 78(13 Supl): 4847.
14.	Tang H, Zhao H, Yu ZY, et al. MicroRNA-194 inhibits cell invasion and migration in hepatocellular carcinoma through PRC1-mediated inhibition of Wnt/β-catenin signaling pathway. Dig Liver Dis, 2019, 51(9): 1314-1322.
15.	Yasen A, Wang M, Ran B, et al. Echinococcus granulosus protoscoleces promotes proliferation and invasion of hepato-cellular carcinoma cells. Cytotechnology, 2021, 73(1): 13-22.
16.	Melsens E, Verberckmoes B, Rosseel N, et al. The VEGFR inhibitor cediranib improves the efficacy of fractionated radiotherapy in a colorectal cancer xenograft model. Eur Surg Res, 2017, 58(3-4): 95-108.
17.	Song Z, Liu T, Chen J, et al. HIF-1α-induced RIT1 promotes liver cancer growth and metastasis and its deficiency increases sensitivity to sorafenib. Cancer Lett, 2019, 460: 96-107.
18.	Li J, Xi W, Li X, et al. Advances in inhibition of protein-protein interactions targeting hypoxia-inducible factor-1 for cancer therapy. Bioorg Med Chem, 2019, 27(7): 1145-1158.
19.	Chen J, Lai L, Liu S, et al. Targeting HIF-1α and VEGF by lentivirus-mediated RNA interference reduces liver tumor cells migration and invasion under hypoxic conditions. Neoplasma, 2016, 63(6): 934-940.
20.	Hayashi Y, Yokota A, Harada H, et al. Hypoxia/pseudohypoxia-mediated activation of hypoxia-inducible factor-1α in cancer. Cancer Sci, 2019, 110(5): 1510-1517.
21.	Ma Z, Xiang X, Li S, et al. Targeting hypoxia-inducible factor-1, for cancer treatment: Recent advances in developing small-molecule inhibitors from natural compounds. Semin Cancer Biol, 2020, 2020 Sep 28. doi: 10.1016/j.semcancer.2020.09.011.
22.	Dewangan J, Srivastava S, Mishra S, et al. Salinomycin inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vitro and in vivo. Biochem Pharmacol, 2019, 164: 326-335.
23.	Ye J, Chen K, Qi L, et al. Metformin suppresses hypoxia-induced migration via the HIF-1α/VEGF pathway in gallbladder cancer in vitro and in vivo. Oncol Rep, 2018, 40(6): 3501-3510.
24.	Chakraborty C, Mitra S, Roychowdhury A, et al. Deregulation of LIMD1-VHL-HIF-1α-VEGF pathway is associated with different stages of cervical cancer. Biochem J, 2018, 475(10): 1793-1806.
25.	Guo LY, Zhu P, Jin XP. Association between the expression of HIF-1α and VEGF and prognostic implications in primary liver cancer. Genet Mol Res, 2016, 15(2). doi: 10.4238/gmr.15028107.

1. Zhu H, Zhang S. Hypoxia inducible factor-1α/vascular endothelial growth factor signaling activation correlates with response to radiotherapy and its inhibition reduces hypoxia-induced angiogenesis in lung cancer. J Cell Biochem, 2018, 119(9): 7707-7718.
2. Zhang B, Li YL, Zhao JL, et al. Hypoxia-inducible factor-1 promotes cancer progression through activating AKT/Cyclin D1 signaling pathway in osteosarcoma. Biomed Pharmacother, 2018, 105: 1-9.
3. Li M, Xie H, Liu Y, et al. Knockdown of hypoxia-inducible factor-1 alpha by tumor targeted delivery of CRISPR/Cas9 system suppressed the metastasis of pancreatic cancer. J Control Release, 2019, 304: 204-215.
4. Koyasu S, Kobayashi M, Goto Y, et al. Regulatory mechanisms of hypoxia-inducible factor 1 activity: two decades of knowledge. Cancer Sci, 2018, 109(3): 560-571.
5. Park SA, Jeong MS, Ha KT, et al. Structure and function of vascular endothelial growth factor and its receptor system. BMB Rep, 2018, 51(2): 73-78.
6. Lenz N, Hirschburger M, Roehrig R, et al. Application of continuous wound-infusion catheters in lung transplantation: a retrospective data analysis. Thorac Cardiovasc Surg, 2017, 65(5): 403-409.
7. Kouvaras E, Christoni Z, Siasios I, et al. Hypoxia-inducible factor 1-alpha and vascular endothelial growth factor in cartilage tumors. Biotech Histochem, 2019, 94(4): 283-289.
8. Tang E, Wang Y, Liu T, et al. Gastrin promotes angiogenesis by activating HIF-1α/β-catenin/VEGF signaling in gastric cancer. Gene, 2019, 704: 42-48.
9. Orbegoso C, Marquina G, George A, et al. The role of cediranib in ovarian cancer. Expert Opin Pharmacother, 2017, 18(15): 1637-1648.
10. Shen S, Luo X, Gao K, et al. Identification and integrative analysis of microRNAs and mRNAs involved in proliferation and invasion of pressure-treated human liver cancer cell lines. Mol Med Rep, 2019, 20(1): 375-387.
11. Liu K, Tian T, Zheng Y, et al. Scutellarin inhibits proliferation and invasion of hepatocellular carcinoma cells via down-regulation of JAK2/STAT3 pathway. J Cell Mol Med, 2019, 23(4): 3040-3044.
12. Momeny M, Sankanian G, Hamzehlou S, et al. Cediranib, an inhibitor of vascular endothelial growth factor receptor kinases, inhibits proliferation and invasion of prostate adenocarcinoma cells. Eur J Pharmacol, 2020, 882: 173298. doi: 10.1016/j.ejphar.2020.173298.
13. Morikawa N, Nilsson MB, Guijarro I, et al. Evaluation of the combination of olaparib and cediranib in small-cell lung cancer cells. Cancer Res, 2018, 78(13 Supl): 4847.
14. Tang H, Zhao H, Yu ZY, et al. MicroRNA-194 inhibits cell invasion and migration in hepatocellular carcinoma through PRC1-mediated inhibition of Wnt/β-catenin signaling pathway. Dig Liver Dis, 2019, 51(9): 1314-1322.
15. Yasen A, Wang M, Ran B, et al. Echinococcus granulosus protoscoleces promotes proliferation and invasion of hepato-cellular carcinoma cells. Cytotechnology, 2021, 73(1): 13-22.
16. Melsens E, Verberckmoes B, Rosseel N, et al. The VEGFR inhibitor cediranib improves the efficacy of fractionated radiotherapy in a colorectal cancer xenograft model. Eur Surg Res, 2017, 58(3-4): 95-108.
17. Song Z, Liu T, Chen J, et al. HIF-1α-induced RIT1 promotes liver cancer growth and metastasis and its deficiency increases sensitivity to sorafenib. Cancer Lett, 2019, 460: 96-107.
18. Li J, Xi W, Li X, et al. Advances in inhibition of protein-protein interactions targeting hypoxia-inducible factor-1 for cancer therapy. Bioorg Med Chem, 2019, 27(7): 1145-1158.
19. Chen J, Lai L, Liu S, et al. Targeting HIF-1α and VEGF by lentivirus-mediated RNA interference reduces liver tumor cells migration and invasion under hypoxic conditions. Neoplasma, 2016, 63(6): 934-940.
20. Hayashi Y, Yokota A, Harada H, et al. Hypoxia/pseudohypoxia-mediated activation of hypoxia-inducible factor-1α in cancer. Cancer Sci, 2019, 110(5): 1510-1517.
21. Ma Z, Xiang X, Li S, et al. Targeting hypoxia-inducible factor-1, for cancer treatment: Recent advances in developing small-molecule inhibitors from natural compounds. Semin Cancer Biol, 2020, 2020 Sep 28. doi: 10.1016/j.semcancer.2020.09.011.
22. Dewangan J, Srivastava S, Mishra S, et al. Salinomycin inhibits breast cancer progression via targeting HIF-1α/VEGF mediated tumor angiogenesis in vitro and in vivo. Biochem Pharmacol, 2019, 164: 326-335.
23. Ye J, Chen K, Qi L, et al. Metformin suppresses hypoxia-induced migration via the HIF-1α/VEGF pathway in gallbladder cancer in vitro and in vivo. Oncol Rep, 2018, 40(6): 3501-3510.
24. Chakraborty C, Mitra S, Roychowdhury A, et al. Deregulation of LIMD1-VHL-HIF-1α-VEGF pathway is associated with different stages of cervical cancer. Biochem J, 2018, 475(10): 1793-1806.
25. Guo LY, Zhu P, Jin XP. Association between the expression of HIF-1α and VEGF and prognostic implications in primary liver cancer. Genet Mol Res, 2016, 15(2). doi: 10.4238/gmr.15028107.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Effects of cediranib on proliferation, migration and invasion of liver cancer cells by inhibiting HIF-1α/VEGF pathway

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