Active metronomic vinorelbine schedules decrease plasma interleukin-2 levels in mice with Lewis lung carcinoma

Abstract

The aim of our study was to investigate the effects of metronomic vinorelbine (mVNR) in a tumor model of Lewis Lung (LL) cancer in immunocompetent C57BL/6 mice, looking at the plasma levels of interleukin-2 (IL-2) and interleukin-8 (IL-8). mVNR caused a concentration-dependent antiproliferative effect in vitro on LL/2 cells. The in vivo experiment showed the significant antitumor effects of mVNR at the dose of 4 mg/Kg and 5 mg/Kg, 3 times/week, and the significant dose-dependent decrease of IL-2 concentrations in plasma samples. Conversely, such an effect was not observed for IL-8. A significant decrease in microvessel density was also found at both the active mVNR doses. In conclusion, our study confirmed the activity of mVNR in an immunocompetent model of lung carcinoma and suggest multiple mechanisms of action, including the modulation of IL-2 levels.

Keywords:

• metronomic chemotherapy
• vinorelbine
• Lewis Lung carcinoma
• interleukine-2
• interleukine-8
• mice

Conflict of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by unconditional funds provided by Pierre Fabre Pharma Srl (Milano, Italy).

Notes on contributors

Paola Orlandi

Paola Orlandi, PhD, is a postdoctoral fellow of the Unit of Pharmacology at the School of Medicine of the University of Pisa.

Marta Banchi

Marta Banchi, Pharm D, is a non-medical resident fellow in Clinical Pharmacology and Toxicology at the University of Pisa.

Greta Alì

Greta AlÌ, MD, is a pathologist at the Pisa University Hospital.

Teresa Di Desidero

Teresa Di Desidero, PharmD, PhD, was a postdoctoral fellow of the Unit of Pharmacology at the School of Medicine of the University of Pisa and now is currently working in the field of clinical trial organization.

Elisabetta Fini

Elisabetta Fini, MD, is a medical resident fellow in Clinical Pharmacology and Toxicology at the University of Pisa.

Gabriella Fontanini

Gabriella Fontanini, MD, is a full professor of Pathological Anatomy at the School of Medicine of University of Pisa.

Guido Bocci

Guido Bocci, MD, PhD, is an associate professor of Pharmacology at the School of Medicine of the University of Pisa. His main scientific interest is related to the preclinical and clinical pharmacology of antineoplastic agents and, in particular, of metronomic chemotherapy.