Dose response of human tumor cells to rhodamine 123 and laser phototherapy.
Previous studies have shown that Rhodamine 123 (Rh123) is an efficient tumor targeting agent for argon laser photodynamic therapy in vitro. Effectiveness of this approach for cancer treatment in vivo will depend on Rh123 tumor uptake kinetics and laser energy delivery via fiberoptics to the tumor site. In the present study, tumor and normal cells were exposed in vitro to 1 micrograms/mL Rh123 until 10%, 50%, and 100% of maximum uptake was achieved. Laser treatment response was monitored by trypan blue exclusion for tumor cell viability and by MTT tetrazolium assays to measure mitochondrial dehydrogenase activity. TE671 fibrosarcoma cells were highly sensitive to argon laser phototherapy (514 nm, 5 W, 1 minute, Tmax = 8 degrees C), with mitochondrial inhibition seen after Rh123 uptake of 12, 50, and 100 ng/million cells. P3 squamous cell carcinoma cells were inhibited 20% and 75% by the laser after Rh123 uptake of 13 or 30 ng/million cells, respectively. M26 melanoma cells were not sensitive to the laser after 15 ng/million cells Rh123 uptake but were inhibited 45% and 75% after Rh123 uptake of 80 and 160 ng/million cells. Micro2 fibroblast mitochondrial activity was reduced less than 25% by the laser after Rh123 uptake of 50 ng/million cells. Cell viability after maximum Rh123 uptake and laser treatment was decreased to 30%, 15%, and 2% for M26 melanoma, P3 squamous cell carcinoma, and TE671 fibrosarcoma cells, but remained over 80% for Micro2 fibroblasts. The results suggest that Rh123 laser treatment response depends on tumor type and drug uptake level, with normal cells being much less sensitive to phototherapy.
Saxton
R E
RE
Division of Surgical Oncology, UCLA School of Medicine 90024.
Haghighat
S
S
Plant
D
D
Lufkin
R
R
Soudant
J
J
Castro
D J
DJ
D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005354:Fibrosarcoma / Q000188:drug therapy / Q000378:metabolism; D005456:Fluorescent Dyes / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D053685:Laser Therapy; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010778:Photochemotherapy; D020112:Rhodamine 123; D012235:Rhodamines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013778:Tetrazolium Salts; D014407:Tumor Cells, Cultured
D000964:Antimetabolites, Antineoplastic; D005456:Fluorescent Dyes; D012235:Rhodamines; D013778:Tetrazolium Salts; D020112:Rhodamine 123