We investigated
tumor regression and the mode of
tumor cell death induced by photodynamic treatment (
PDT) with
chlorin p(6) (Cp(6)) in hamster cheek pouch model of
oral squamous cell carcinoma. Cp(6) was administered systemically through
intraperitoneal injection and after 4h the
tumors were subjected to photodynamic treatment using red light (660±25nm, fluence ∼100J/cm(2)).
Tumor response to
PDT was monitored by measuring the
tumor volume before
PDT and 1week after. Results show that smaller
tumors (⩽80mm(3)) regressed completely after
PDT with Cp(6) dose of 2.0mg/kg
body weight and for the bigger
tumors (∼180mm(3)) higher dose of Cp(6) (4.0mg/kg) was more effective.
Tumors treated with lower Cp(6) dose showed infiltration of immune cells, absence of TUNEL labeling, smeared pattern of DNA fragmentation and no significant increase in
caspase-3 activity suggestive of necrotic cell death and
inflammation. In
tumors treated with higher Cp(6) dose, features characteristic of apoptotic cell death such as extensive TUNEL positive labeling, increase in
caspase-3 activity and laddered pattern of DNA fragmentation were observed and there was no infiltration of immune cells.
PDT with Cp(6) was also found to lead to expression of matrix metalloprotease-9 (MMP-9) which was greater at lower
drug dose
PDT as compared to higher
drug dose
PDT. These results suggest that
drug dose plays an important role in determining the mechanism of
tumor cell death and effectiveness of
PDT.