Interferon-alpha and -gamma in combination with chemotherapeutic drugs: in vitro sensitivity studies in four human mesothelioma cell lines

Our plain-English summary of Interferon-alpha and -gamma in combination with chemotherapeutic drugs: in vitro sensitivity studies in four human mesothelioma cell lines, by A.M. Hand, K. Husgafvel-Pursiainen, K. Pelin, et al (Anti-cancer Drugs, 1992).

The study

• Authors: A.M. Hand, K. Husgafvel-Pursiainen, K. Pelin, M. Vallas, T. Suitiala, A. Ekman, M. Mattson, K. Mattson, K. Linnainmaa
• Journal: Anti-cancer Drugs
• Published: 1992;3(6):687-94
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mesothelioma is a tumor of the serous surfaces in the thorax and abdomen. This tumor has proved to be exceptionally resistant to treatment, although a variety of multi-modality therapies have been tried. We have used four human mesothelioma cell lines, originating from diffuse asbestos-related malignant (pleural) mesothelioma, to assess in vitro sensitivity to five chemotherapeutic drugs, to recombinant human interferon (IFN)-alpha and -gamma and to combined immuno-chemotherapy. The cytotoxic effects were assayed by vital dye exclusion. The drugs tested were etoposide, cisplatin, mitoxantrone, 4-epirubicin and vindesine. The combinations tested were etoposide+cisplatin, and etoposide+cisplatin+mitoxantrone. All the drugs and combinations were also tested with recombinant human (rHu) IFN-alpha 2C (rHuIFN-alpha), rHuIFN-gamma, and rHuIFN-alpha+rHuIFN-gamma. The cell lines were most sensitive to mitoxantrone, 4-epirubicin and vindesine (TC50 < or = 0.001 micrograms/ml), and least sensitive to etoposide and cisplatin (TC50 > or = 0.1 micrograms/ml) used singly. There was no improvement in sensitivity when the drugs were combined. To further investigate the lack of response to cisplatin treatment, we examined the binding of cisplatin to the mesothelioma cell DNA. The tumor cell DNA bound markedly less cisplatin than human fetal fibroblast DNA. Three cell lines were tested with rHuIFN-alpha and rHuIFN-gamma on their own or rHuIFN-alpha+rHuIFN-gamma. They were consistently sensitive to rHuIFN-alpha, but the sensitivity to rHuIFN-gamma varied with the cell lines. Finally, we tested two cell lines with the drugs singly and in combination, together with 0.01 micrograms/ml each of rHuIFN-alpha and rHuIFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS)

In plain English

This was a laboratory study of cancer cells grown in dishes, not a study of patients. Researchers at the Institute of Occupational Health in Helsinki used four cell lines grown from asbestos-related malignant pleural mesothelioma. Three came from the untreated primary tumors of patients. The fourth, M9K, came from a tumor that had spread, in a patient previously treated with mitoxantrone and radiotherapy. They exposed the cells to five chemotherapy drugs (etoposide, cisplatin, mitoxantrone, 4-epirubicin and vindesine), to laboratory-made interferon-alpha and interferon-gamma, and to combinations, then counted the surviving cells. The cells were insensitive to cisplatin and relatively sensitive to mitoxantrone and 4-epirubicin. Combining drugs did not improve the effect over single drugs. Adding both interferons increased growth inhibition. For example, a cisplatin dose that inhibited M38K cells by 50% alone inhibited them by 65% with interferon. DNA from the mesothelioma cells bound clearly less platinum from cisplatin than DNA from normal fetal fibroblast cells. The authors concluded that their findings suggest mitoxantrone, 4-epirubicin and interferon should be studied further in developing mesothelioma therapy.

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 human mesothelioma cell lines (drug and interferon sensitivity testing, plus cisplatin DNA-binding measurements)
• Who was studied: Four human mesothelioma cell lines established in the authors' laboratory in Helsinki, Finland, from tumors described as diffuse asbestos-related malignant (pleural) mesothelioma. Three lines (M14K, M33K, M38K) came from the primary tumors of previously untreated patients. One line (M9K) came from a metastatic tumor of a patient previously treated with mitoxantrone and radiotherapy. Human fetal fibroblasts were used as normal control cells.
• Exposure: Laboratory exposure of the cells to etoposide, cisplatin, mitoxantrone, 4-epirubicin and vindesine; to recombinant human interferon-alpha and interferon-gamma; to the combinations etoposide + cisplatin and etoposide + cisplatin + mitoxantrone; and to drugs combined with 0.01 micrograms per ml of each interferon. Asbestos exposure was not studied; it is only described as the origin of the tumors.
• Main results:
  • Series 1 (three primary tumor cell lines, 48 h): all three were insensitive to cisplatin, with a 50% toxic concentration (TC50) above 0.75 micrograms per ml
  • Series 1: the three cell lines were relatively sensitive to mitoxantrone and 4-epirubicin (TC50 below 0.06 micrograms per ml)
  • Series 1: sensitivity to vindesine showed no consistent pattern
  • TC50 values for the normal human fetal fibroblast control cells were generally lower; the data were not shown
  • Series 2 (cell lines M38K and M9K): TC50 for cisplatin and etoposide was above 0.5 micrograms per ml, and for mitoxantrone below 0.006 micrograms per ml
  • Both M38K and M9K showed greater anti-proliferation with interferon-alpha and interferon-gamma combined than with either interferon alone; the effect was much more marked for M9K
  • In M38K cells, 1.3 micrograms per ml of cisplatin inhibited the cells by 50% alone and by 65% with interferon added
  • In M9K cells, 0.004 micrograms per ml of mitoxantrone inhibited the cells by 50% alone and by 80% with interferon
  • Drug combinations (etoposide + cisplatin; etoposide + cisplatin + mitoxantrone) gave no improvement in cytotoxicity over the individual drugs
  • Adding both interferons raised growth inhibition by etoposide + cisplatin from 50% to 65% for M38K and to 75% for M9K
  • For etoposide + cisplatin + mitoxantrone, the authors reported that adding interferons did not significantly increase growth inhibition for M38K, but raised it from 50% to 80% for M9K
  • Platinum bound to the DNA of mesothelioma cells (M14K, M33K, M38K) after cisplatin treatment was clearly less than that bound to normal fibroblast DNA
  • The metastatic, previously treated cell line M9K was more sensitive to all the drugs and to interferon than the primary tumor cell line M38K
• The authors' conclusion: The authors concluded that their in vitro findings, together with clinical experience, suggest that mitoxantrone, 4-epirubicin and interferon should be studied further in developing mesothelioma therapy.
• Limitations the authors state:
  • The authors noted that the TC50 values for M38K differed slightly between the two series of experiments, possibly because of the longer treatment time in the second series, which may also explain the greater variation in other 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: Mesothelioma, Thorax, Chemotherapy, Cisplatin, Fibroblast.

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