mTHPC-mediated photodynamic treatment of Lewis lung carcinoma in vitro and in vivo

Daiva Dabkevičienė¹, Vaidotas Stankevičius¹, Gražina Graželienė², Arvydas Markuckas¹, Janina Didžiapetrienė², Vida Kirvelienė¹

¹Department of Biochemistry and Biophysics, Vilnius University, ²Institute of Oncology, Vilnius University, Lithuania

Key words: photodynamic treatment; LLC1 cell line; Lewis lung carcinoma; photosensitizer; mTHPC.

Summary. Background and objective. The ongoing search for the enhancement of efficacy of photodynamic therapy stimulates the interest in molecular mechanisms of the response to the treatment. Looking for the cell line suitable for investigation of cellular response both in vivo and in vitro, we evaluated phototoxicity of m-tetrakis-(3-hydroxyphenyl)-chlorin (mTHPC) on viability of Lewis lung carcinoma (LLC1) cells in vitro, growth of murine transplantable tumor, and mice survival.

Material and methods. LLC1 cell culture and male C57BL/6 mice bearing Lewis lung carcinoma were used for the experiments. Photodynamic treatment was mediated by m-tetrakis-(3-hydroxyphenyl)-chlorin as a photosensitizer. Light emitting diode array was used for illumination. The effect of the photodynamic treatment was evaluated by comparison of viability of control and treated cells, growth of tumors, and survival of the control and treated mice.

Results. In vitro, a cytotoxic dose inducing a reduction in viability of LLC1 cells by 50% was achieved at 60 mJ/cm² and approximately 400 ng/mL of the photosensitizer, or 30 mJ/cm² and 600 ng/mL of mTHPC. Both the concentration of the photosensitizer and duration of light exposure were significant determinants of cytotoxic effect. In vivo, an injection of 0.25 mg/kg of mTHPC to mice bearing Lewis lung tumor and illumination at 120 J/cm² taking place after 24 h significantly inhibited tumor growth and prolonged mice survival. However, the tumors regained their growth potential after 9 days.

Conclusions. Photodynamic treatment mediated by m-tetrakis-(3-hydroxyphenyl)-chlorin had a significant effect on LLC1 cells in vitro and growth of Lewis lung carcinoma in vivo.

Correspondence to V. Kirvelienė, Department of Biochemistry and Biophysics, Vilnius University, M. K. Čiurlionio 21/27, 03101 Vilnius, Lithuania. E-mail: vida.kirveliene@gf.vu.lt

Received 10 February 2009, accepted 7 May 2010