Evaluation for Synergistic Effects by Combinations of Photodynamic Therapy (PDT) with Temoporfin (mTHPC) and Pt(II) Complexes Carboplatin, Cisplatin or Oxaliplatin in a Set of Five Human Cancer Cell Lines.

ABSTRACT

The platinum(II) complexes carboplatin (CBDCA), cisplatin (CDDP) and oxaliplatin (1-OHP) are used as anticancer drugs in a large number of tumour chemotherapy regimens. Many attempts have been made to combine Pt(II)-based chemotherapy with alternative treatment strategies. One such alternative anticancer approach is known as photodynamic therapy (PDT), where a non-toxic photosensitizer (PS) produces oxidative stress via the formation of reactive oxygen species (ROS) after local illumination of the affected tissue. A very promising PS is 5,10,15,20-tetra(m-hydroxyphenyl)chlorin (mTHPC, Temoporfin), which is approved for the treatment of head and neck cancer in Europe. In the present study, a combination of mTHPC-mediated PDT and either CBDCA, CDDP, or 1-OHP was applied to five human cancer cell lines from different tumour origins. Cytotoxicity was determined by the MTT assay and synergistic effects on cytotoxicity were evaluated by calculation of Combination Indices (CI). Synergy was identified in some of the combinations, for example, with 1-OHP in three of the tested cell lines but antagonism was also observed for a number of combinations in certain cell lines. In cases of synergy, elevated ROS levels were observed after combination but apoptosis induction was not necessarily increased compared to a treatment with a single compound. Cell cycle analysis revealed a formation of apoptotic subG1 populations and S phase as well as G2/M phase arrests after combination. In conclusion, pre-treatment with mTHPC-PDT has the potential to sensitize some types of tumour cells towards Pt(II) complexes, in particular 1-OHP but synergy is highly dependent on the type of cancer.