In vitro sensitivity of normal human mesothelial and malignant mesothelioma cell lines to four new chemotherapeutic agents

Our plain-English summary of In vitro sensitivity of normal human mesothelial and malignant mesothelioma cell lines to four new chemotherapeutic agents, by T. Ollikainen, A. Knuuttila, S. Suhonen, et al (Anti-cancer Drugs, 2000).

The study

• Authors: T. Ollikainen, A. Knuuttila, S. Suhonen, M. Taavitsainen, A. Jekunen, K. Mattson, K. Linnainmaa
• Journal: Anti-cancer Drugs
• Published: 2000;11(2):93-9
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In this study, we used four human mesothelioma cell lines (M14K, M24K, M25K and M38K), one transformed human mesothelial cell line (MeT-5A) and one primary mesothelial culture (UPL) to test for in vitro sensitivity to docetaxel, paclitaxel, SN-38 [an active metabolite of irinotecan (CPT-11)] and gemcitabine, as single agents. Subconfluent cell cultures were treated with 2x10(-9), 5x10(-9), 10(-8), 2x10(-8) and 5x10(-8) M concentrations of each drug for 48 h. The sensitivity was measured in terms of cell viability using the Trypan blue exclusion method. All four drugs were potent inhibitors of mesothelioma cell growth, but cell lines from different patients diverged in their sensitivity to the individual agents. In most cases docetaxel, paclitaxel and SN-38 were more potent killers of mesothelioma cells than gemcitabine. The induction of DNA damage was investigated using the Comet assay; cells from two cell lines (M14K and M25K) were treated with subtoxic 10(-8) M concentrations of each drug for 4, 24 and 48 h. Each of the agents caused a slight increase in DNA single-strand breaks at a concentration of 10(-8) M.

In plain English

This was a laboratory study of cells grown in dishes, not of patients. The authors used four cell lines from human malignant mesothelioma tumors (M14K, M24K, M25K and M38K), a transformed human mesothelial cell line (MeT-5A), and primary mesothelial cells from non-malignant pleural fluid (UPL). Cells were exposed for 48 hours to docetaxel, paclitaxel, SN-38 (an active breakdown product of irinotecan) or gemcitabine at five concentrations, and the living cells were counted. At 10 to the minus 8 molar, responses differed by cell line. With SN-38, the number of living cells was 13% of the untreated control count for M14K, 14% for M25K and 93% for M24K. Gemcitabine was the least active drug in most cell lines, though SN-38 was less active in M24K. A DNA damage test (the Comet assay) found significant increases in DNA strand breaks from all four drugs in both tested mesothelioma cell lines after 24 hours. These increases were not significantly higher than those from the positive control. The authors concluded that all four drugs inhibited mesothelioma cell growth, with differing potency, and that these methods could help select drugs for clinical trials.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: In vitro laboratory study of drug sensitivity in cultured cell lines (preclinical), using a cell viability test (Trypan blue exclusion) and a DNA damage test (Comet assay)
• Who was studied: Four previously established human malignant mesothelioma cell lines (M14K from an epithelial subtype tumor; M24K, M25K and M38K from mixed subtype tumors), one SV-40 transformed, non-tumourigenic human mesothelial cell line (MeT-5A), and primary mesothelial cells (UPL) from non-malignant pleural effusions of patients at Helsinki University Central Hospital (heart failure or inflammatory disease). Dates not given.
• Exposure: Four chemotherapy drugs, each given alone: docetaxel, paclitaxel, SN-38 and gemcitabine. For viability tests the concentrations were 2 x 10 to the minus 9, 5 x 10 to the minus 9, 10 to the minus 8, 2 x 10 to the minus 8 and 5 x 10 to the minus 8 M for 48 h. For the Comet assay the concentration was 10 to the minus 8 M for 4, 24 and 48 h. Asbestos exposure was not studied.
• Main results:
  • All viability figures are the number of living cells in treated cultures expressed as a percentage of the living cells in untreated control cultures (control = 100%).
  • Docetaxel at 10 to the minus 8 M: M25K was the most sensitive mesothelioma cell line (20% viability relative to control) and M24K the most resistant (56% viability relative to control).
  • Paclitaxel at 10 to the minus 8 M: viability relative to control was 34% in M38K (most affected) and 57% in M14K (most resistant).
  • SN-38 at 10 to the minus 8 M: living cells were 13% of the control count in M14K and 14% in M25K, but 93% in M24K (most resistant).
  • In most cases docetaxel, paclitaxel and SN-38 were more potent than gemcitabine against the mesothelioma cells. The ranking was not the same in every cell line.
  • In the M24K cell line at 10 to the minus 8 M, the order of activity was paclitaxel, then docetaxel, then gemcitabine, then SN-38, so SN-38 was the least active drug in that line.
  • The authors described the taxanes (docetaxel and paclitaxel) as the most active agents in the non-malignant cell lines.
  • The non-malignant control cells were sensitive to all doses of docetaxel.
  • Comet assay: after 24 h, all four drugs caused significant increases in DNA damage (mean tail moment) in both tested mesothelioma cell lines (M14K and M25K).
  • Comet assay: after 48 h, no DNA damage was detected in M14K cells with any of the four drugs.
  • The increases in tail moment were not significantly higher than those caused by the positive control, hydrogen peroxide.
• The authors' conclusion: The authors concluded that all four drugs inhibited mesothelioma cell growth but differed noticeably in potency. They also concluded that the cell viability test and Comet assay would be especially useful for selecting drugs for clinical trials in rare diseases such as mesothelioma.
• Limitations the authors state:
  • The authors noted that the Comet assay results were not comparable to the 48 h cell viability test results.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Mesothelioma, Mesothelial Cells, Gemcitabine, Comet Assay.

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