Issue

Vol. 66 No. 1: Issue 1

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

Liposomal clodronate combined with Cisplatin or Sorafenib inhibits hepatocellular carcinoma cell proliferation, migration and invasion by suppressing FOXQ1 expression

https://doi.org/10.14715/cmb/2019.66.1.8
Yilong Zhou
Department of liver Surgery/Liver Transplantation Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
Yuan Chen
Department of Surgery, Nantong Tumor Hospital, Nantong, 226300, China
Chunyang Ma
Department of Surgery, Nantong Tumor Hospital, Nantong, 226300, China
Bingfeng Shao
Department of Surgery, Nantong Tumor Hospital, Nantong, 226300, China
Feng Zhang
Department of liver Surgery/Liver Transplantation Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China

Corresponding Author(s) : Feng Zhang

igrd59@163.com

Cellular and Molecular Biology, Vol. 66 No. 1: Issue 1

Abstract

The purpose of this study was to investigate the effect of liposomal clodronate combined with Cisplatin or Sorafenib on the FOXQ1 expression and biological function of hepatocellular carcinoma cell lines.  The expression of FOXQ1 was determined in normal hepatic cell line and hepatocellular carcinoma cell lines using quantitative real-time polymerase chain reaction (qRT-PCR). HepG2 and MHCC97H cells were administered low, medium and high concentrations of cisplatin (3, 5 and 7 μg/ml) or Sorafenib (2, 7 and 20 μg/ml) in combination with liposomal clodronate (LC, 20μg/ml), and the expression of FOXQ1 in each group was determined. Cell migration, MTT and transwell assays were used to determine the effects of the treatments on biological functions of HepG2 and MHCC97H cells. qRT-PCR showed that the expression of FOXQ1 mRNA was higher in the four hepatocellular carcinoma cell lines than in normal cells, and the expression of FOXQ1 mRNA in HepG2 and MHCC97H cells were more dominant. All the tested doses of Cisplatin, but only high dose Sorafenib down-regulated the expression of FOXQ1. However, Sorafenib at low and medium concentrations had no significant effect on the expression of FOXQ1. When Cisplatin or Sorafenib was administered in combination with LC, the expression level of FOXQ1 was significantly reduced. Cell migration, MTT and transwell assays showed that proliferation, migration and invasion were inhibited when each drug was administered alone, but was stronger when the drugs were combined with liposomal clodronate.
Liposomal clodronate combined with Cisplatin or Sorafenib down-regulates the expression of FOXQ1 in HepG2 and MHCC97H hepatoma cells, and inhibits their proliferation, migration and invasion.

Keywords

FOXQ1 Cisplatin Sorafenib Liposomal clodronate.
Zhou, Y., Chen, Y., Ma, C., Shao, B., & Zhang, F. (2020). Liposomal clodronate combined with Cisplatin or Sorafenib inhibits hepatocellular carcinoma cell proliferation, migration and invasion by suppressing FOXQ1 expression. Cellular and Molecular Biology, 66(1), 49–54. https://doi.org/10.14715/cmb/2019.66.1.8
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. Lin CW, Chen YS, Lin CC, Lee PH, Lo GH, Hsu CC, et al. Significant predictors of overall survival in patients with hepatocellular carcinoma after surgical resection. PLoS One 2018; 13: 0202650.
  2. Goh GB, Chang PE, Tan CK. Changing epidemiology of hepatocellular carcinoma in Asia. Best Pract Res Clin Gastroenterol 2015; 29: 919-928.
  3. Gupta MK, Atkinson J, McGlynn P. DNA structure specificity conferred on a replicative helicase by its loader. J Biol Chem 2010; 285: 979-987.
  4. Song P, Feng X, Zhang K, Song T, Ma K, Kokudo N, et al. Screening for and surveillance of high-risk patients with HBV-related chronic liver disease: promoting the early detection of hepatocellular carcinoma in China. Biosci Trends 2013; 7: 1-6.
  5. Karaman B, Battal B, Sari S, Verim S. Hepatocellular carcinoma review: current treatment, and evidence-based medicine. World J Gastroenterol 2014; 20: 18059-18060.
  6. Jiao D, Li Z, Zhu M, Wang Y, Wu G, Han X. LncRNA MALAT1 promotes tumor growth and metastasis by targeting miR-124/foxq1 in bladder transitional cell carcinoma (BTCC). Am J Cancer Res 2018; 8: 748-760.
  7. Qin A, Zhu J, Liu X, Zeng D, Gu M, Lv C. MicroRNA-1271 inhibits cellular proliferation of hepatocellular carcinoma. Oncol Lett 2017; 14: 6783-6788.
  8. Sadahiro S, Suzuki T, Tanaka A, Okada K, Kamata H, Koisumi J. Clinical significance of and future perspectives for hepatic arterial infusion chemotherapy in patients with liver metastases from colorectal cancer. Surg Today 2013; 43: 1088-1094.
  9. Chen CH, Chen MC, Wang JC, Tsai AC, Chen CS, Liou JP, et al. Synergistic interaction between the HDAC inhibitor, MPT0E028, and sorafenib in liver cancer cells in vitro and in vivo. Clin Cancer Res 2014; 20: 1274-1287.
  10. Gao J, Rong Y, Huang Y, Shi P, Wang X, Meng X, et al. Cirrhotic stiffness affects the migration of hepatocellular carcinoma cells and induces sorafenib resistance through YAP. J Cell Physiol 2019; 234: 2639-2648.
  11. Zhen L, Chen J, Yong F, Han X, Pan HM, Han WD. The Efficacy and Safety of Apatinib Treatment for Patients with Unresectable or Relapsed Liver Cancer: a retrospective study. J Cancer 2018; 9: 2773-2777.
  12. Motwani MP, Gilroy DW. Macrophage development and polarization in chronic inflammation. Semin Immunol 2015; 27: 257-266.
  13. Canan CH, Gokhale NS, Carruthers B, Lafuse WP, Schlesinger LS, Torrelles JB, et al. Characterization of lung inflammation and its impact on macrophage function in aging. J Leukoc Biol 2014; 96: 473-480.
  14. Guth AM, Hafeman SD, Elmslie RE, Dow SW. Liposomal clodronate treatment for tumour macrophage depletion in dogs with soft-tissue sarcoma. Vet Comp Oncol 2013; 11: 296-305.
  15. Abdul-Cader MS, Ehiremen G, Nagy E, Abdul-Careem MF. Low pathogenic avian influenza virus infection increases the staining intensity of KUL01+ cells including macrophages yet decrease of the staining intensity of KUL01+ cells using clodronate liposomes did not affect the viral genome loads in chickens. Vet Immunol Immunopathol 2018; 198: 37-43.
  16. Su YW, Hung CY, Lam HB, Chang YC, Yang PS. A Single Institution Experience of Incorporation of Cisplatin into Adjuvant Chemotherapy for Patients With Triple-Negative Breast Cancer of Unknown BRCA Mutation Status. Clin Med Insights Oncol 2018; 12: 1179554918794672.
  17. Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 2014; 740: 364-378.
  18. Wilmes A, Bielow C, Ranninger C, Bellwon P, Aschauer L, Limonciel A, et al. Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics. Toxicol In Vitro 2015; 30: 117-127.
  19. He C, Dong X, Zhai B, Jiang X, Dong D, Li B, et al. MiR-21 mediates sorafenib resistance of hepatocellular carcinoma cells by inhibiting autophagy via the PTEN/Akt pathway. Oncotarget 2015; 6: 28867-28881.
  20. Kuczynski EA, Lee CR, Man S, Chen E, Kerbel RS. Effects of Sorafenib Dose on Acquired Reversible Resistance and Toxicity in Hepatocellular Carcinoma. Cancer Res 2015; 75: 2510-2519.
  21. Tarlock K, Chang B, Cooper T, Gross T, Gupta S, Neudorf S, et al. Sorafenib treatment following hematopoietic stem cell transplant in pediatric FLT3/ITD acute myeloid leukemia. Pediatr Blood Cancer 2015; 62: 1048-1054.
  22. Franck C, Rosania R, Franke S, Haybaeck J, Canbay A, Venerito M. The BRAF Status May Predict Response to Sorafenib in Gastrointestinal Stromal Tumors Resistant to Imatinib, Sunitinib, and Regorafenib: Case Series and Review of the Literature. Digestion 2018; 99: 1-6.
  23. Xu J, Li J, Chen J, Liu ZJ. Effect of adjuvant interferon therapy on hepatitis b/c virus-related hepatocellular carcinoma after curative therapy - meta-analysis. Adv Clin Exp Med 2015; 24: 331-340.
  24. Zhang YQ, Guo JS. Antiviral therapies for hepatitis B virus-related hepatocellular carcinoma. World J Gastroenterol 2015; 21: 3860-3866.
  25. Chen L, Zhao H, Yang X, Gao JY, Cheng J. HBsAg-negative hepatitis B virus infection and hepatocellular carcinoma. Discov Med 2014; 18: 189-193.
  26. Peng XH, Huang HR, Lu J, Liu X, Zhao FP, Zhang B, et al. MiR-124 suppresses tumor growth and metastasis by targeting Foxq1 in nasopharyngeal carcinoma. Mol Cancer 2014; 13: 186.
  27. Zhang Z, Ma J, Luan G, Kang L, Su Y, He Y, et al. MiR-506 suppresses tumor proliferation and invasion by targeting FOXQ1 in nasopharyngeal carcinoma. PLoS One 2015; 10: 0122851.
  28. Pei Y, Wang P, Liu H, He F, Ming L. FOXQ1 promotes esophageal cancer proliferation and metastasis by negatively modulating CDH1. Biomed Pharmacother 2015; 74: 89-94.
  29. Meng F, Speyer CL, Zhang B, Zhao Y, Chen W, Gorski DH, et al. PDGFRalpha and beta play critical roles in mediating Foxq1-driven breast cancer stemness and chemoresistance. Cancer Res 2015; 75: 584-593.
  30. Wang W, He S, Ji J, Huang J, Zhang S, Zhang Y. The prognostic significance of FOXQ1 oncogene overexpression in human hepatocellular carcinoma. Pathol Res Pract 2013; 209: 353-358.
  31. Peng X, Luo Z, Kang Q, Deng D, Wang Q, Peng H, et al. FOXQ1 mediates the crosstalk between TGF-beta and Wnt signaling pathways in the progression of colorectal cancer. Cancer Biol Ther 2015; 16: 1099-1109.
  32. Xia L, Huang W, Tian D, Zhang L, Qi X, Chen Z, et al. Forkhead box Q1 promotes hepatocellular carcinoma metastasis by transactivating ZEB2 and VersicanV1 expression. Hepatology 2014; 59: 958-973.
  33. Guo J, Yan Y, Yan Y, Guo Q, Zhang M, Zhang J, et al. Tumor-associated macrophages induce the expression of FOXQ1 to promote epithelial-mesenchymal transition and metastasis in gastric cancer cells. Oncol Rep 2017; 38: 2003-2010.
  34. Krause TA, Alex AF, Engel DR, Kurts C, Eter N. VEGF-production by CCR2-dependent macrophages contributes to laser-induced choroidal neovascularization. PLoS One 2014; 9: 94313.
  35. Haque MR, Lee DY, Ahn CH, Jeong JH, Byun Y. Local co-delivery of pancreatic islets and liposomal clodronate using injectable hydrogel to prevent acute immune reactions in a type 1 diabetes. Pharm Res 2014; 31: 2453-2462.
  36. Davison NL, Gamblin AL, Layrolle P, Yuan H, de Bruijn JD, Barrère-de Groot F. Liposomal clodronate inhibition of osteoclastogenesis and osteoinduction by submicrostructured beta-tricalcium phosphate. Biomaterials 2014; 35: 5088-5097.
  37. Zhang W, Zhu XD, Sun HC, Xiong YQ, Zhuang PY, Xu HX. Depletion of tumor-associated macrophages enhances the effect of sorafenib in metastatic liver cancer models by antimetastatic and antiangiogenic effects. Clin Cancer Res 2010; 16: 3420-3430.
Read More
Author biographies is not available.
Crossref
Scopus
Google Scholar
Europe PMC
Download this PDF file
PDF
Statistic
Read Counter : 801 Download : 439