Assessment of the Chemosensitivity of Uveal Melanoma Cells Ex Vivo

Bull Exp Biol Med. 2020 Nov;170(1):142-147. doi: 10.1007/s10517-020-05020-3. Epub 2020 Nov 24.

Abstract

The study was designed to create a primary cell culture of uveal melanoma and to evaluate its resistance to chemotherapy. Of the obtained 20 samples of uveal melanoma, the primary cultures with proliferation sufficient for MTT test were derived in only 7 cases. However, even these cultures were unable to survive more than 4 passages; the cells accumulated melanin and underwent apoptosis. Retinol palmitate and nepafenac produced no cytotoxic effect on uveal melanoma cells. Of 5 cultures treated with sodium valproate (Convulex), no pronounced cytotoxic effect was observed in one culture (UM4); in 2 cultures, 50% cells died in the presence of the lowest drug concentration of 1.88 mg/ml; and in 2 cultures, the same effect was achieved at drug concentrations 7-10 mg/ml. The cytotoxic effect of treosulfan was evaluated in only 4 cultures of uveal melanoma: the drug exhibited pronounced antitumor activity on all cultures, in 2 cases, it was effective at a concentration of 0.16 mg/ml. Gemcitabine in a concentration of 2.5 mg/ml produced a pronounced cytotoxic effect in 4 out of 7 cultures (death of 70-80% cells) and induced death of ~45% cells in the remaining 3 cultures. Mitoxantrone had ambiguous effect: in 2 of 5 cultures, the drug in high concentrations stimulated the growth of tumor cells, but in 3 cultures, the drug even in minimum concentrations induced death of 70-80% cells.

Keywords: MTT test; cell culture; chemotherapy; uveal melanoma.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / pharmacology*
  • Benzeneacetamides / pharmacology*
  • Busulfan / analogs & derivatives*
  • Busulfan / pharmacology
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Choroid Neoplasms / drug therapy
  • Choroid Neoplasms / pathology
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Diterpenes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Gemcitabine
  • Humans
  • Male
  • Melanoma / drug therapy
  • Melanoma / pathology
  • Middle Aged
  • Phenylacetates / pharmacology*
  • Primary Cell Culture
  • Retinyl Esters / pharmacology*
  • Tumor Cells, Cultured
  • Uveal Neoplasms / drug therapy
  • Uveal Neoplasms / pathology
  • Valproic Acid / pharmacology*

Substances

  • Antineoplastic Agents
  • Benzeneacetamides
  • Diterpenes
  • Phenylacetates
  • Retinyl Esters
  • nepafenac
  • Deoxycytidine
  • retinol palmitate
  • Valproic Acid
  • treosulfan
  • Busulfan
  • Gemcitabine

Supplementary concepts

  • Uveal melanoma