Enhancing Anti-Tumor Activity of Sorafenib Mesoporous Silica Nanomatrix in Metastatic Breast Tumor and Hepatocellular Carcinoma via the Co-Administration with Flufenamic Acid

Int J Nanomedicine. 2020 Mar 16:15:1809-1821. doi: 10.2147/IJN.S240436. eCollection 2020.

Abstract

Introduction: Because tumor-associated inflammation is a hallmark of cancer treatment, in the present study, sorafenib mesoporous silica nanomatrix (MSNM@SFN) co-administrated with flufenamic acid (FFA, a non-steroidal anti-inflammatory drug (NSAID)) was investigated to enhance the anti-tumor activity of MSNM@SFN.

Methods: Metastatic breast tumor 4T1/luc cells and hepatocellular carcinoma HepG2 cells were selected as cell models. The effects of FFA in vitro on cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in 4T1/luc and HepG2 cells were investigated. The in vivo anti-tumor activity of MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) was evaluated in a 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model, respectively.

Results: The results indicated that FFA could markedly decrease cell migration, PGE2 secretion, and AKR1C1 and AKR1C3 levels in both 4T1/luc and HepG2 cells. The enhanced anti-tumor activity of MSNM@SFN+FFA compared with that of MSNM@SFN was confirmed in the 4T1/luc metastatic tumor model, HepG2 tumor-bearing nude mice model, and HepG2 orthotopic tumor-bearing nude mice model in vivo, respectively.

Discussion: MSNM@SFN co-administrating with FFA (MSNM@SFN+FFA) developed in this study is an alternative strategy for improving the therapeutic efficacy of MSNM@SFN via co-administration with NSAIDs.

Keywords: 4T1/luc; AKR1C1; AKR1C3; FFA; HepG2; MSNM@SFN; PGE2; flufenamic acid; sorafenib mesoporous silica nanomatrix.

MeSH terms

  • 20-Hydroxysteroid Dehydrogenases / metabolism
  • Aldo-Keto Reductase Family 1 Member C3 / metabolism
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal* / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / pharmacology
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Dinoprostone / metabolism
  • Female
  • Flufenamic Acid / administration & dosage
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanostructures / administration & dosage
  • Nanostructures / chemistry
  • Silicon Dioxide / chemistry
  • Sorafenib / administration & dosage
  • Xenograft Model Antitumor Assays

Substances

  • 20-Hydroxysteroid Dehydrogenases
  • 3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase
  • AKR1C3 protein, human
  • Aldo-Keto Reductase Family 1 Member C3
  • Anti-Inflammatory Agents, Non-Steroidal
  • Dinoprostone
  • Flufenamic Acid
  • Silicon Dioxide
  • Sorafenib